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Keywords: p53
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Articles

Structure and function of MDM2 and MDM4 in health and disease

Ivy Yiyi Zhu, Alec Lloyd, William R. Critchley, Queen Saikia, Dhananjay Jade, Aysha Divan, Elton Zeqiraj, Michael A. Harrison, Christopher J. Brown, Sreenivasan Ponnambalam
Journal: Biochemical Journal
Biochem J (2025) 482 (04): 241–262.
https://doi.org/10.1042/BCJ20240757
Published: 17 February 2025
..., play central roles in cellular homeostasis. MDM-linked dysfunction is associated with an increased risk of oncogenesis, primarily through targeting the tumor suppressor protein p53 for ubiquitination and degradation. Recent studies have revealed multifaceted roles of MDM proteins that are p53...
View articletitled, Structure and function of MDM2 and MDM4 in health and disease
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Articles

Glut1 expression is increased by p53 reduction to switch metabolism to glycolysis during osteoblast differentiation

Tomokazu Ohnishi, Joji Kusuyama, Kenjiro Bandow, Tetsuya Matsuguchi
Journal: Biochemical Journal
Biochem J (2020) 477 (10): 1795–1811.
https://doi.org/10.1042/BCJ20190888
Published: 21 May 2020
... osteoblasts increased expressions of glycolysis-related enzymes such as Glut1, hexokinase 1 and 2, lactate dehydrogenase A and pyruvate kinase M2 during their differentiation. Osteoblast differentiation decreased expression of tumor suppressor p53, which negatively regulates Glut1 expression, and enhanced...
View articletitled, Glut1 expression is increased by p53 reduction to switch metabolism to glycolysis during osteoblast differentiation
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Includes: Supplementary data
Articles

Hereditary hemochromatosis disrupts uric acid homeostasis and causes hyperuricemia via altered expression/activity of xanthine oxidase and ABCG2

Bojana Ristic, Sathish Sivaprakasam, Monisha Narayanan, Vadivel Ganapathy
Journal: Biochemical Journal
Biochem J (2020) 477 (8): 1499–1513.
https://doi.org/10.1042/BCJ20190873
Published: 29 April 2020
...; however, there was an increase in Mrp4 and a decrease in Abcg2 in Hfe −/− mice. As ABCG2 mediates intestinal excretion of UA and mutations in ABCG2 cause hyperuricemia, we examined the potential connection between iron and ABCG2. We found p53-responsive elements in h ABCG2 promoter and confirmed...
View articletitled, Hereditary hemochromatosis disrupts uric acid homeostasis and causes hyperuricemia via altered expression/activity of xanthine oxidase and ABCG2
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Includes: Supplementary data
Articles

Biophysical characterization of p53 core domain aggregates

Igor Lima, Ambuja Navalkar, Samir K. Maji, Jerson L. Silva, Guilherme A.P. de Oliveira, Elio A. Cino
Journal: Biochemical Journal
Biochem J (2020) 477 (1): 111–120.
https://doi.org/10.1042/BCJ20190778
Published: 08 January 2020
..., such as oligomers and amyloid fibrils. p53 is an essential tumor suppressor that is prone to such conformational transitions, resulting in its compromised ability to avert cancer. This work explores the biophysical properties of early-, mid-, and late-stage p53 core domain (p53C) aggregates. Atomistic and coarse...
View articletitled, Biophysical characterization of p53 core domain aggregates
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Articles

Allosteric changes in HDM2 by the ATM phosphomimetic S395D mutation: implications on HDM2 function

Lukas Uhrik, Lixiao Wang, Lucia Haronikova, Ixaura Medina-Medina, Yolanda Rebolloso-Gomez, Sa Chen, Borivoj Vojtesek, Robin Fahraeus, Lenka Hernychova, Vanesa Olivares-Illana
Journal: Biochemical Journal
Biochem J (2019) 476 (21): 3401–3411.
https://doi.org/10.1042/BCJ20190687
Published: 15 November 2019
... with intrinsic disorder regions. HDM2 is a hub protein with a large interactome and with different cellular functions. It is best known for its regulation of the p53 tumour suppressor. Under normal cellular conditions, HDM2 ubiquitinates and degrades p53 by the 26S proteasome but after DNA damage, HDM2 switches...
View articletitled, Allosteric changes in HDM2 by the ATM phosphomimetic S395D mutation: implications on HDM2 function
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Includes: Supplementary data
Articles

Nutlin-3 plus tanshinone IIA exhibits synergetic anti-leukemia effect with imatinib by reactivating p53 and inhibiting the AKT/mTOR pathway in Ph+ ALL

Yong Guo, Yi Li, Bing Xiang, Xiao-Ou Huang, Hong-Bing Ma, Fang-Fang Wang, Yu-Ping Gong
Journal: Biochemical Journal
Biochem J (2017) 474 (24): 4153–4170.
https://doi.org/10.1042/BCJ20170386
Published: 06 December 2017
... of growth-signaling pathways and protective feedback signaling of leukemia cells in response to TKI treatment. Continuous activation of AKT/mTOR signaling and inactivation of p53 pathway were two mechanisms of TKI resistance. Here, we reported that nutlin-3 plus tanshinone IIA significantly potentiated...
View articletitled, Nutlin-3 plus tanshinone IIA exhibits synergetic anti-leukemia effect with imatinib by reactivating p53 and inhibiting the AKT/mTOR pathway in Ph+ ALL
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Includes: Supplementary data
Articles

Post-transcriptional regulation of the tumor suppressor p53 by a novel miR-27a, with implications during hypoxia and tumorigenesis

Raihana Maqbool, Saife Niaz Lone, Mahboob Ul Hussain
Journal: Biochemical Journal
Biochem J (2016) 473 (20): 3597–3610.
https://doi.org/10.1042/BCJ20160359
Published: 11 October 2016
...Raihana Maqbool; Saife Niaz Lone; Mahboob Ul Hussain The tumor suppressor protein p53 is intricately regulated by various signaling molecules, including non-coding small RNAs, called microRNAs (miRNAs). The in silico analysis and the inverse expression status in various cell lines raised...
View articletitled, Post-transcriptional regulation of the tumor suppressor p53 by a novel miR-27a, with implications during hypoxia and tumorigenesis
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Includes: Supplementary data
Articles

Unravelling the mechanisms regulating muscle mitochondrial biogenesis

David A. Hood, Liam D. Tryon, Heather N. Carter, Yuho Kim, Chris C.W. Chen
Journal: Biochemical Journal
Biochem J (2016) 473 (15): 2295–2314.
https://doi.org/10.1042/BCJ20160009
Published: 28 July 2016
... of the Biochemical Society 2016 aging calcium signalling exercise exercise training mitochondrial protein import mitochondrial reticulum mitophagy mtDNA muscle disuse p53 PPARγ co-activator-1α (PGC-1α) reactive oxygen species Tfam Tfeb The mitochondrial content of any tissue is one...
View articletitled, Unravelling the mechanisms regulating muscle mitochondrial biogenesis
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Articles

c-Abl-mediated tyrosine phosphorylation of JunB is required for Adriamycin-induced expression of p21

Noritaka Yamaguchi, Ryuzaburo Yuki, Sho Kubota, Kazumasa Aoyama, Takahisa Kuga, Yuuki Hashimoto, Takeshi Tomonaga, Naoto Yamaguchi
Journal: Biochemical Journal
Biochem J (2015) 471 (1): 67–77.
https://doi.org/10.1042/BJ20150372
Published: 21 September 2015
... to be required for expression of the cell cycle inhibitor p21 upon Adriamycin stimulation. Adriamycin AP1 transcription factor c-Abl cyclin-dependent kinase inhibitor DNA-damage response JunB p21 p53 DDR (DNA-damage response) is activated by genotoxic stress caused by various stimuli...
View articletitled, c-Abl-mediated tyrosine phosphorylation of JunB is required for Adriamycin-induced expression of p21
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Includes: Supplementary data
Articles

Regulation of the p53 response and its relationship to cancer

David W. Meek
Journal: Biochemical Journal
Biochem J (2015) 469 (3): 325–346.
https://doi.org/10.1042/BJ20150517
Published: 23 July 2015
...David W. Meek p53 has been studied intensively as a major tumour suppressor that detects oncogenic events in cancer cells and eliminates them through senescence (a permanent non-proliferative state) or apoptosis. Consistent with this role, p53 activity is compromised in a high proportion of all...
View articletitled, Regulation of the p53 response and its relationship to cancer
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Articles

DNA polymerase η is regulated by poly(rC)-binding protein 1 via mRNA stability

Cong Ren, Seong-Jun Cho, Yong-Sam Jung, Xinbin Chen
Journal: Biochemical Journal
Biochem J (2014) 464 (3): 377–386.
https://doi.org/10.1042/BJ20141164
Published: 05 December 2014
...Cong Ren; Seong-Jun Cho; Yong-Sam Jung; Xinbin Chen POLH (DNA polymerase η), a target of p53 tumour suppressor, plays a key role in TLS (translesion DNA synthesis). Loss of POLH is responsible for the human cancer-prone syndrome XPV (xeroderma pigmentosum variant). Owing to its critical role in DNA...
View articletitled, DNA polymerase η is regulated by poly(rC)-binding protein 1 via mRNA stability
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Articles

Drp1 stabilizes p53 on the mitochondria to trigger necrosis under oxidative stress conditions in vitro and in vivo

Xing Guo, Hiromi Sesaki, Xin Qi
Journal: Biochemical Journal
Biochem J (2014) 461 (1): 137–146.
https://doi.org/10.1042/BJ20131438
Published: 13 June 2014
.... In the present study, we showed that Drp1 (dynamin-related protein 1), a primary mitochondrial fission protein, stabilizes the well-known stress gene p53 and is required for p53 translocation to the mitochondria under conditions of oxidative stress. We found that Drp1 binding to p53 induced mitochondria-related...
View articletitled, Drp1 stabilizes p53 on the mitochondria to trigger necrosis under oxidative stress conditions in vitro and in vivo
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Includes: Supplementary data
Articles

Identification of TP53-induced glycolysis and apoptosis regulator (TIGAR) as the phosphoglycolate-independent 2,3-bisphosphoglycerate phosphatase

Isabelle Gerin, Gaëtane Noël, Jennifer Bolsée, Olivier Haumont, Emile Van Schaftingen, Guido T. Bommer
Journal: Biochemical Journal
Biochem J (2014) 458 (3): 439–448.
https://doi.org/10.1042/BJ20130841
Published: 28 February 2014
...Isabelle Gerin; Gaëtane Noël; Jennifer Bolsée; Olivier Haumont; Emile Van Schaftingen; Guido T. Bommer The p53-induced protein TIGAR [TP53 (tumour protein 53)-induced glycolysis and apoptosis regulator] is considered to be a F26BPase (fructose-2,6-bisphosphatase) with an important role in cancer...
View articletitled, Identification of TP53-induced glycolysis and apoptosis regulator (TIGAR) as the phosphoglycolate-independent 2,3-bisphosphoglycerate phosphatase
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Articles

Heat-shock factor 1 both positively and negatively affects cellular clonogenic growth depending on p53 status

Chau H. Nguyen, Benjamin J. Lang, Ryan C. C. Chai, Jessica L. Vieusseux, Michelle M. Kouspou, John T. Price
Journal: Biochemical Journal
Biochem J (2013) 452 (2): 321–329.
https://doi.org/10.1042/BJ20130098
Published: 10 May 2013
... progression. We examined the role of HSF1 in relation to cancer cell clonogenicity, an important attribute of cancer cells. Ectopic expression or HSF1 knockdown demonstrated that HSF1 positively regulated cancer cell clonogenic growth. Furthermore, knockdown of mutant p53 indicated that HSF1 actions were...
View articletitled, Heat-shock factor 1 both positively and negatively affects cellular clonogenic growth depending on p53 status
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Articles

Golgi-SNARE GS28 potentiates cisplatin-induced apoptosis by forming GS28–MDM2–p53 complexes and by preventing the ubiquitination and degradation of p53

Nian-Kang Sun, Shang-Lang Huang, Kun-Yi Chien, Chuck C.-K. Chao
Journal: Biochemical Journal
Biochem J (2012) 444 (2): 303–314.
https://doi.org/10.1042/BJ20112223
Published: 11 May 2012
...Nian-Kang Sun; Shang-Lang Huang; Kun-Yi Chien; Chuck C.-K. Chao In the present study, we observed that the Golgi-SNARE (soluble N -ethylmaleimide-sensitive fusion protein-attachment protein receptor) GS28 forms a complex with p53 in HEK (human embryonic kidney)-293 cells. Given that p53 represents...
View articletitled, Golgi-SNARE GS28 potentiates cisplatin-induced apoptosis by forming GS28–MDM2–p53 complexes and by preventing the ubiquitination and degradation of p53
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Includes: Supplementary data
Articles

p53 Ser 15 phosphorylation disrupts the p53–RPA70 complex and induces RPA70-mediated DNA repair in hypoxia

Esha Madan, Rajan Gogna, Uttam Pati
Journal: Biochemical Journal
Biochem J (2012) 443 (3): 811–820.
https://doi.org/10.1042/BJ20111627
Published: 16 April 2012
...Esha Madan; Rajan Gogna; Uttam Pati Cellular stressors are known to inhibit the p53–RPA70 (replication protein A, 70 kDa subunit) complex, and RPA70 increases cellular DNA repair in cancer cells. We hypothesized that regulation of RPA70-mediated DNA repair might be responsible for the inhibition...
View articletitled, p53 Ser 15 phosphorylation disrupts the p53–RPA70 complex and induces RPA70-mediated DNA repair in hypoxia
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Includes: Supplementary data
Articles

Transforming growth factor β1 represses proximal tubular cell microRNA-192 expression through decreased hepatocyte nuclear factor DNA binding

Robert H. Jenkins, John Martin, Aled O. Phillips, Timothy Bowen, Donald J. Fraser
Journal: Biochemical Journal
Biochem J (2012) 443 (2): 407–416.
https://doi.org/10.1042/BJ20111861
Published: 27 March 2012
... nuclear factor) and p53 binding sites within this region that were required for constitutive promoter activity, which was decreased by TGF-β1 through an Alk5-dependent mechanism. TGF-β1 treatment decreased HNF binding to the miR-194-2/192 promoter, whereas knockdown of HNF-1 inhibited mature miR-192...
View articletitled, Transforming growth factor β1 represses proximal tubular cell microRNA-192 expression through decreased hepatocyte nuclear factor DNA binding
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Includes: Supplementary data
Articles

Metabolic oxidative stress elicited by the copper(II) complex [Cu(isaepy) 2 ] triggers apoptosis in SH-SY5Y cells through the induction of the AMP-activated protein kinase/p38 MAPK /p53 signalling axis: evidence for a combined use with 3-bromopyruvate in neuroblastoma treatment

Giuseppe Filomeni, Simone Cardaci, Ana Maria Da Costa Ferreira, Giuseppe Rotilio, Maria Rosa Ciriolo
Journal: Biochemical Journal
Biochem J (2011) 437 (3): 443–453.
https://doi.org/10.1042/BJ20110510
Published: 13 July 2011
.../p53-mediated apoptosis in tumour cells by targeting mitochondria. In the present study, we found that p38 MAPK (p38 mitogen-activated protein kinase) is the molecular link in the phosphorylation cascade connecting AMPK to p53. Transfection of SH-SY5Y cells with a dominant-negative mutant of AMPK...
View articletitled, Metabolic oxidative stress elicited by the copper(II) complex [Cu(isaepy) 2 ] triggers apoptosis in SH-SY5Y cells through the induction of the AMP-activated protein kinase/p38 MAPK /p53 signalling axis: evidence for a combined use with 3-bromopyruvate in neuroblastoma treatment
Open the PDF for Metabolic oxidative stress elicited by the copper(II) complex [Cu(isaepy) 2 ] triggers apoptosis in SH-SY5Y cells through the induction of the AMP-activated protein kinase/p38 MAPK /p53 signalling axis: evidence for a combined use with 3-bromopyruvate in neuroblastoma treatment in another window
Includes: Supplementary data
Articles

The RNA-binding protein HuR stabilizes survivin mRNA in human oesophageal epithelial cells

James M. Donahue, Elizabeth T. Chang, Lan Xiao, Peng-Yuan Wang, Jaladanki N. Rao, Douglas J. Turner, Jian-Ying Wang, Richard J. Battafarano
Journal: Biochemical Journal
Biochem J (2011) 437 (1): 89–96.
https://doi.org/10.1042/BJ20110028
Published: 14 June 2011
.... This was associated with decreased survivin mRNA and promoter activity, suggesting a decrease in transcription. Levels of p53, a negative transcriptional regulator of survivin, increased following HuR overexpression, in conjunction with enhanced p53 mRNA stability. Silencing p53 prior to HuR overexpression resulted...
View articletitled, The RNA-binding protein HuR stabilizes survivin mRNA in human oesophageal epithelial cells
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Articles

ATR (ataxia telangiectasia mutated- and Rad3-related kinase) is activated by mild hypothermia in mammalian cells and subsequently activates p53

Anne Roobol, Jo Roobol, Martin J. Carden, Amandine Bastide, Anne E. Willis, Warwick B. Dunn, Royston Goodacre, C. Mark Smales
Journal: Biochemical Journal
Biochem J (2011) 435 (2): 499–508.
https://doi.org/10.1042/BJ20101303
Published: 29 March 2011
... cycle at the upper range (31–33 °C) and its complete arrest at the lower range (27–28 °C) of mild hypothermia is effected by the activation of p53 and subsequent expression of p21. However, the mechanism by which cold is perceived in mammalian cells with the subsequent activation of p53 has remained...
View articletitled, ATR (ataxia telangiectasia mutated- and Rad3-related kinase) is activated by mild hypothermia in mammalian cells and subsequently activates p53
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Includes: Supplementary data
Articles

The diverse members of the mammalian HSP70 machine show distinct chaperone-like activities

Jurre Hageman, Maria A.W.H. van Waarde, Alicja Zylicz, Dawid Walerych, Harm H. Kampinga
Journal: Biochemical Journal
Biochem J (2011) 435 (1): 127–142.
https://doi.org/10.1042/BJ20101247
Published: 15 March 2011
..., as purified HSPA6 could not chaperone heat-unfolded luciferase but was able to assist in reactivation of heat-unfolded p53. So, even within the highly sequence-conserved HSPA family, functional differentiation is larger than expected, with HSPA6 being an extreme example that may have evolved to maintain...
View articletitled, The diverse members of the mammalian HSP70 machine show distinct chaperone-like activities
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Includes: Supplementary data
Articles

p14 ARF inhibits the functions of adenovirus E1A oncoprotein

Jia Shen, Shengping Zhang, Yang Li, Wen Zhang, Jiandong Chen, Mary Zhang, Ting Wang, Ling Jiang, Xiuqun Zou, Jiemin Wong, Xiaotao Li, Yongping Cui, Chuangui Wang
Journal: Biochemical Journal
Biochem J (2011) 434 (2): 275–285.
https://doi.org/10.1042/BJ20101163
Published: 11 February 2011
... checkpoint’ function through both p53-dependent and p53-independent mechanisms. In the present study, we demonstrate a novel p53-independent interaction between p14 ARF and the adenovirus oncoprotein E1A. p14 ARF inhibits E1A transcriptional function and promotes ubiquitination-dependent degradation of E1A...
View articletitled, p14 ARF inhibits the functions of adenovirus E1A oncoprotein
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Articles

p38 MAPK /p53 signalling axis mediates neuronal apoptosis in response to tetrahydrobiopterin-induced oxidative stress and glucose uptake inhibition: implication for neurodegeneration

Simone Cardaci, Giuseppe Filomeni, Giuseppe Rotilio, Maria R. Ciriolo
Journal: Biochemical Journal
Biochem J (2010) 430 (3): 439–451.
https://doi.org/10.1042/BJ20100503
Published: 27 August 2010
... commitment in SH-SY5Y neuroblastoma cells and in mouse primary cortical neurons. We identified in p38 MAPK /p53 a BH4-responsive pro-apoptotic signalling axis, as demonstrated by the recovery of neuronal viability achieved by gene silencing or pharmacological inhibition of both p38 MAPK and p53. BH4-induced...
View articletitled, p38 MAPK /p53 signalling axis mediates neuronal apoptosis in response to tetrahydrobiopterin-induced oxidative stress and glucose uptake inhibition: implication for neurodegeneration
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Includes: Supplementary data
Articles

DNA damage signalling recruits RREB-1 to the p53 tumour suppressor promoter

Hanshao Liu, Hoi Chin Hew, Zheng-Guang Lu, Tomoko Yamaguchi, Yoshio Miki, Kiyotsugu Yoshida
Journal: Biochemical Journal
Biochem J (2009) 422 (3): 543–551.
https://doi.org/10.1042/BJ20090342
Published: 27 August 2009
...Hanshao Liu; Hoi Chin Hew; Zheng-Guang Lu; Tomoko Yamaguchi; Yoshio Miki; Kiyotsugu Yoshida Transcriptional regulation of the p53 tumour suppressor gene plays an important role in the control of the expression of various target genes involved in the DNA damage response. However, the molecular basis...
View articletitled, DNA damage signalling recruits RREB-1 to the p53 tumour suppressor promoter
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Articles

A novel p53 target gene, S100A9 , induces p53-dependent cellular apoptosis and mediates the p53 apoptosis pathway

Chunsun Li, Hongyan Chen, Fang Ding, Yu Zhang, Aiping Luo, Mingrong Wang, Zhihua Liu
Journal: Biochemical Journal
Biochem J (2009) 422 (2): 363–372.
https://doi.org/10.1042/BJ20090465
Published: 13 August 2009
... previous work showed that S100A9 was severely down-regulated in human ESCC (oesophageal squamous cell carcinoma). To further investigate the transcriptional regulation of S100A9, we analysed the S100A9 promoter region and found several putative p53BS (p53-binding sites). Luciferase reporter assays showed...
View articletitled, A novel p53 target gene, S100A9 , induces p53-dependent cellular apoptosis and mediates the p53 apoptosis pathway
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Includes: Supplementary data
Articles

Role of Mdm2 acid domain interactions in recognition and ubiquitination of the transcription factor IRF-2

Susanne Pettersson, Michael Kelleher, Emmanuelle Pion, Maura Wallace, Kathryn L. Ball
Journal: Biochemical Journal
Biochem J (2009) 418 (3): 575–585.
https://doi.org/10.1042/BJ20082087
Published: 25 February 2009
...Susanne Pettersson; Michael Kelleher; Emmanuelle Pion; Maura Wallace; Kathryn L. Ball Mdm2 (murine double minute 2)-mediated ubiquitination of the p53 tumour suppressor requires interaction of the ligase at two distinct binding sites that form general multiprotein-docking sites for the p53 protein...
View articletitled, Role of Mdm2 acid domain interactions in recognition and ubiquitination of the transcription factor IRF-2
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Articles

The tumour suppressor p53 regulates the expression of amyloid precursor protein (APP)

Ascensión Cuesta, Alberto Zambrano, María Royo, Angel Pascual
Journal: Biochemical Journal
Biochem J (2009) 418 (3): 643–650.
https://doi.org/10.1042/BJ20081793
Published: 25 February 2009
... that p53 regulates the expression of the APP gene in neuroblastoma cells. Transient expression of ectopic p53, activation of endogenous p53 by the DNA-damaging drug camptothecin or Mdm2 (murine double minute 2) depletion decreases the intracellular levels of APP in murine N2aβ neuroblastoma cells...
View articletitled, The tumour suppressor p53 regulates the expression of amyloid precursor protein (APP)
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Articles

Ankyrin repeats-containing cofactors interact with ADA3 and modulate its co-activator function

Chia-Wei Li, Gia Khanh Dinh, Aihua Zhang, J. Don Chen
Journal: Biochemical Journal
Biochem J (2008) 413 (2): 349–357.
https://doi.org/10.1042/BJ20071484
Published: 26 June 2008
... on nuclear receptors, whereas ANCO-1 stimulated p53-mediated transactivation. These data suggest that ADA3 is a newly identified target of the ANCO proteins, which may modulate co-activator function in a transcription-factor-specific manner. 1 Present address: Merck Research Laboratories, 126 E...
View articletitled, Ankyrin repeats-containing cofactors interact with ADA3 and modulate its co-activator function
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Articles

DNA topology influences p53 sequence-specific DNA binding through structural transitions within the target sites

Eva B. Jagelská, Václav Brázda, Petr Pečinka, Emil Paleček, Miroslav Fojta
Journal: Biochemical Journal
Biochem J (2008) 412 (1): 57–63.
https://doi.org/10.1042/BJ20071648
Published: 25 April 2008
...Eva B. Jagelská; Václav Brázda; Petr Pečinka; Emil Paleček; Miroslav Fojta The tumour suppressor protein p53 is one of the most important factors regulating cell proliferation, differentiation and programmed cell death in response to a variety of cellular stress signals. P53 is a nuclear...
View articletitled, DNA topology influences p53 sequence-specific DNA binding through structural transitions within the target sites
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Articles

The 7-amino-acid site in the proline-rich region of the N-terminal domain of p53 is involved in the interaction with FAK and is critical for p53 functioning

Vita M. Golubovskaya, Richard Finch, Min Zheng, Elena V. Kurenova, William G. Cance
Journal: Biochemical Journal
Biochem J (2008) 411 (1): 151–160.
https://doi.org/10.1042/BJ20071657
Published: 13 March 2008
...Vita M. Golubovskaya; Richard Finch; Min Zheng; Elena V. Kurenova; William G. Cance It is known that p53 alterations are commonly found in tumour cells. Another marker of tumorigenesis is FAK (focal adhesion kinase), a non-receptor kinase that is overexpressed in many types of tumours. Previously...
View articletitled, The 7-amino-acid site in the proline-rich region of the N-terminal domain of p53 is involved in the interaction with FAK and is critical for p53 functioning
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Articles

Deacetylation of the retinoblastoma tumour suppressor protein by SIRT1

Sharon Wong, Jason D. Weber
Journal: Biochemical Journal
Biochem J (2007) 407 (3): 451–460.
https://doi.org/10.1042/BJ20070151
Published: 12 October 2007
... to the SIRT1-targeted domain of the p53 tumour suppressor protein. Cultures of arrested cells, via contact inhibition or DNA damage, exhibited decreased Rb phosphorylation and increased Rb acetylation. Overexpression of SIRT1 in either confluent or etoposide-treated cells resulted in a significant reduction...
View articletitled, Deacetylation of the retinoblastoma tumour suppressor protein by SIRT1
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Articles

Oxidative stress regulates IGF1R expression in vascular smooth-muscle cells via p53 and HDAC recruitment

Mary M. Kavurma, Nichola Figg, Martin R. Bennett, John Mercer, Levon M. Khachigian, Trevor D. Littlewood
Journal: Biochemical Journal
Biochem J (2007) 407 (1): 79–87.
https://doi.org/10.1042/BJ20070380
Published: 12 September 2007
... is inhibited by ectopic expression of IGF1R. Oxidative stress repressed IGF1R expression at multiple levels, and this was also blocked by mutant p53. Oxidative stress also induced p53 phosphorylation and apoptosis in VSMCs. p53 negatively regulated IGF1R promoter activity and expression and, consistent...
View articletitled, Oxidative stress regulates IGF1R expression in vascular smooth-muscle cells via p53 and HDAC recruitment
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Articles

p53 regulates its own activator: transcriptional co-activator PC4 , a new p53-responsive gene

A. Hari Kishore, Kiran Batta, Chandrima Das, Shipra Agarwal, Tapas K. Kundu
Journal: Biochemical Journal
Biochem J (2007) 406 (3): 437–444.
https://doi.org/10.1042/BJ20070390
Published: 29 August 2007
...A. Hari Kishore; Kiran Batta; Chandrima Das; Shipra Agarwal; Tapas K. Kundu The tumour suppressor protein p53 regulates the expression of several genes that mediate cell cycle arrest, apoptosis, DNA repair and other cellular responses. Recently, we have shown that human transcriptional co-activator...
View articletitled, p53 regulates its own activator: transcriptional co-activator PC4 , a new p53-responsive gene
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Includes: Supplementary data
Articles

Transient arrest in proteasomal degradation during inhibition of translation in the unfolded protein response

Marina Shenkman, Sandra Tolchinsky, Maria Kondratyev, Gerardo Z. Lederkremer
Journal: Biochemical Journal
Biochem J (2007) 404 (3): 509–516.
https://doi.org/10.1042/BJ20061854
Published: 29 May 2007
... of cytosolic substrates (p53 and p27 kip1 ) and of those targeted to ER (endoplasmic reticulum)-associated degradation (uncleaved precursor of asialoglycoprotein receptor H2a). Degradation resumed soon after the protein synthesis arrest that occurs in early UPR subsided. Consistent with this, protein synthesis...
View articletitled, Transient arrest in proteasomal degradation during inhibition of translation in the unfolded protein response
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Articles

Interference with energy metabolism by 5-aminoimidazole-4-carboxamide-1-β-D-ribofuranoside induces HPV suppression in cervical carcinoma cells and apoptosis in the absence of LKB11

Julia Nafz, Johanna De-Castro Arce, Verena Fleig, Andrea Patzelt, Sybille Mazurek, Frank Rösl
Journal: Biochemical Journal
Biochem J (2007) 403 (3): 501–510.
https://doi.org/10.1042/BJ20061053
Published: 12 April 2007
... leads to a reduced binding affinity of the transcription factor AP-1 (activator protein-1) and in turn to a selective suppression of HPV transcription. Moreover, the outcome of AICAR on proliferation and survival was dependent on p53 activation and the presence of LKB1, the major upstream kinase of AMPK...
View articletitled, Interference with energy metabolism by 5-aminoimidazole-4-carboxamide-1-β-D-ribofuranoside induces HPV suppression in cervical carcinoma cells and apoptosis in the absence of LKB11
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Includes: Supplementary data
Articles

Differential regulation of human YY1 and caspase 7 promoters by prohibitin through E2F1 and p53 binding sites

B. Joshi, S. Rastogi, M. Morris, L. M. Carastro, C. Decook, E. Seto, S. P. Chellappan
Journal: Biochemical Journal
Biochem J (2007) 401 (1): 155–166.
https://doi.org/10.1042/BJ20060364
Published: 11 December 2006
... bind to and enhance the transcriptional activity of p53. Here, we show that promoters of human YY1 (Yin and Yang 1) as well as caspase 7 genes are modulated by prohibitin. YY1 promoter activity was reduced upon overexpression of prohibitin, while it was enhanced when prohibitin was depleted by small...
View articletitled, Differential regulation of human YY1 and caspase 7 promoters by prohibitin through E2F1 and p53 binding sites
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Articles

Tumour suppressor p53 down-regulates the expression of the human hepatocyte nuclear factor 4α (HNF4α) gene

Yutaka Maeda, Wendy W. Hwang-Verslues, Gang Wei, Takuya Fukazawa, Mary L. Durbin, Laurie B. Owen, Xuan Liu, Frances M. Sladek
Journal: Biochemical Journal
Biochem J (2006) 400 (2): 303–313.
https://doi.org/10.1042/BJ20060614
Published: 14 November 2006
...Yutaka Maeda; Wendy W. Hwang-Verslues; Gang Wei; Takuya Fukazawa; Mary L. Durbin; Laurie B. Owen; Xuan Liu; Frances M. Sladek The liver is exposed to a wide variety of toxic agents, many of which damage DNA and result in increased levels of the tumour suppressor protein p53. We have previously...
View articletitled, Tumour suppressor p53 down-regulates the expression of the human hepatocyte nuclear factor 4α (HNF4α) gene
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Articles

Destabilizing missense mutations in the tumour suppressor protein p53 enhance its ubiquitination in vitro and in vivo

Harumi Shimizu, David Saliba, Maura Wallace, Lee Finlan, Patrick R. R. Langridge-Smith, Ted R. Hupp
Journal: Biochemical Journal
Biochem J (2006) 397 (2): 355–367.
https://doi.org/10.1042/BJ20051521
Published: 28 June 2006
...Harumi Shimizu; David Saliba; Maura Wallace; Lee Finlan; Patrick R. R. Langridge-Smith; Ted R. Hupp p53 ubiquitination catalysed by MDM2 (murine double minute clone 2 oncoprotein) provides a biochemical assay to dissect stages in E3-ubiquitin-ligase-catalysed ubiquitination of a conformationally...
View articletitled, Destabilizing missense mutations in the tumour suppressor protein p53 enhance its ubiquitination in vitro and in vivo
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Articles

A novel ARF-binding protein (LZAP) alters ARF regulation of HDM2

Jialiang Wang, Xiaping He, Ying Luo, Wendell G. Yarbrough
Journal: Biochemical Journal
Biochem J (2006) 393 (2): 489–501.
https://doi.org/10.1042/BJ20050960
Published: 23 December 2005
...Jialiang Wang; Xiaping He; Ying Luo; Wendell G. Yarbrough The tumour suppressor ARF (alternative reading frame) is encoded by the INK4a (inhibitor of cyclin-dependent kinase 4)/ ARF locus, which is frequently altered in human tumours. ARF binds MDM2 (murine double minute 2) and releases p53 from...
View articletitled, A novel ARF-binding protein (LZAP) alters ARF regulation of HDM2
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Articles

Cancer cells activate p53 in response to 10-formyltetrahydrofolate dehydrogenase expression

Natalia V. Oleinik, Natalia I. Krupenko, David G. Priest, Sergey A. Krupenko
Journal: Biochemical Journal
Biochem J (2005) 391 (3): 503–511.
https://doi.org/10.1042/BJ20050533
Published: 25 October 2005
... is selectively cytotoxic to cancer cells. We have recently shown that ectopic expression of FDH in A549 lung cancer cells induces G1 arrest and apoptosis that was accompanied by elevation of p53 and its downstream target, p21. It was not known, however, whether FDH-induced apoptosis is p53-dependent...
View articletitled, Cancer cells activate p53 in response to 10-formyltetrahydrofolate dehydrogenase expression
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Articles

Physical and functional interactions between members of the tumour suppressor p53 and the Sp families of transcription factors: importance for the regulation of genes involved in cell-cycle arrest and apoptosis

George Koutsodontis, Eleftheria Vasilaki, Wan-Chih Chou, Paraskevi Papakosta, Dimitris Kardassis
Journal: Biochemical Journal
Biochem J (2005) 389 (2): 443–455.
https://doi.org/10.1042/BJ20041980
Published: 05 July 2005
...George Koutsodontis; Eleftheria Vasilaki; Wan-Chih Chou; Paraskevi Papakosta; Dimitris Kardassis In the present study, we have investigated mechanisms of transcriptional co-operation between proteins that belong to the tumour suppressor p53 and Sp (specificity protein) families of transcription...
View articletitled, Physical and functional interactions between members of the tumour suppressor p53 and the Sp families of transcription factors: importance for the regulation of genes involved in cell-cycle arrest and apoptosis
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Articles

PARP inhibition sensitizes p53-deficient breast cancer cells to doxorubicin-induced apoptosis

José Antonio MUÑOZ-GÁMEZ, David MARTÍN-OLIVA, Rocío AGUILAR-QUESADA, Ana CAÑUELO, M. Isabel NUÑEZ, M. Teresa VALENZUELA, J. M. RUIZ de ALMODÓVAR, Gilbert de MURCIA, F. Javier OLIVER
Journal: Biochemical Journal
Biochem J (2005) 386 (1): 119–125.
https://doi.org/10.1042/BJ20040776
Published: 08 February 2005
...José Antonio MUÑOZ-GÁMEZ; David MARTÍN-OLIVA; Rocío AGUILAR-QUESADA; Ana CAÑUELO; M. Isabel NUÑEZ; M. Teresa VALENZUELA; J. M. RUIZ de ALMODÓVAR; Gilbert de MURCIA; F. Javier OLIVER p53 deficiency confers resistance to doxo (doxorubicin), a clinically active and widely used antitumour anthracycline...
View articletitled, PARP inhibition sensitizes p53-deficient breast cancer cells to doxorubicin-induced apoptosis
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Articles

Exploitation of KESTREL to identify NDRG family members as physiological substrates for SGK1 and GSK3

James T. MURRAY, David G. CAMPBELL, Nicholas MORRICE, Gillian C. AULD, Natalia SHPIRO, Rodolpho MARQUEZ, Mark PEGGIE, Jenny BAIN, Graham B. BLOOMBERG, Florian GRAHAMMER, Florian LANG, Peer WULFF, Dietmar KUHL, Philip COHEN
Journal: Biochemical Journal
Biochem J (2004) 384 (3): 477–488.
https://doi.org/10.1042/BJ20041057
Published: 07 December 2004
... (NDRG) p53 phosphorylation serum- and glucocorticoid-induced kinase 1 (SGK1) SGK1 (serum- and glucocorticoid-induced kinase 1) is an immediate early gene whose level of expression is greatly enhanced within 1 h of exposing most cells to serum, glucocorticoids or other agonists (reviewed...
View articletitled, Exploitation of KESTREL to identify NDRG family members as physiological substrates for SGK1 and GSK3
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Articles

Alternative reading frame protein (ARF)-independent function of CARF (collaborator of ARF) involves its interactions with p53: evidence for a novel p53-activation pathway and its negative feedback control

M. Kamrul HASAN, Tomoko YAGUCHI, Yasumasu MINODA, Takashi HIRANO, Kazunari TAIRA, Renu WADHWA, Sunil C. KAUL
Journal: Biochemical Journal
Biochem J (2004) 380 (3): 605–610.
https://doi.org/10.1042/bj20040337
Published: 15 June 2004
...M. Kamrul HASAN; Tomoko YAGUCHI; Yasumasu MINODA; Takashi HIRANO; Kazunari TAIRA; Renu WADHWA; Sunil C. KAUL CARF, a c ollaborator of ARF (alternative reading frame protein), was cloned as a novel ARF-binding protein from a yeast-interaction screen. It potentiated ARF-mediated p53 function...
View articletitled, Alternative reading frame protein (ARF)-independent function of CARF (collaborator of ARF) involves its interactions with p53: evidence for a novel p53-activation pathway and its negative feedback control
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Articles

p300 relieves p53-evoked transcriptional repression of hypoxia-inducible factor-1 (HIF-1)

Tobias SCHMID, Jie ZHOU, Roman KÖHL, Bernhard BRÜNE
Journal: Biochemical Journal
Biochem J (2004) 380 (1): 289–295.
https://doi.org/10.1042/bj20031299
Published: 15 May 2004
... Hippel–Lindau protein)-dependent ubiquitination and subsequent 26 S-proteasomal degradation of HIF-1α. Besides HIF-1, the transcription factor and tumour suppressor p53 accumulates and is activated under conditions of prolonged/severe hypoxia. Recently, the interaction between p53 and HIF-1α was reported...
View articletitled, p300 relieves p53-evoked transcriptional repression of hypoxia-inducible factor-1 (HIF-1)
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Articles

Activation of the DNA-binding ability of latent p53 protein by protein kinase C is abolished by protein kinase CK2

Šárka POSPÍŠILOVÁ, Václav BRÁZDA, Kateřina KUCHAŘÍKOVÁ, M. Gloria LUCIANI, Ted R. HUPP, Petr SKLÁDAL, Emil PALEČEK, Bořivoj VOJTĚŠEK
Journal: Biochemical Journal
Biochem J (2004) 378 (3): 939–947.
https://doi.org/10.1042/bj20030662
Published: 15 March 2004
...Šárka POSPÍŠILOVÁ; Václav BRÁZDA; Kateřina KUCHAŘÍKOVÁ; M. Gloria LUCIANI; Ted R. HUPP; Petr SKLÁDAL; Emil PALEČEK; Bořivoj VOJTĚŠEK p53 is one of the most important regulators of cell proliferation and differentiation and of programmed cell death, triggering growth arrest and/or apoptosis...
View articletitled, Activation of the DNA-binding ability of latent p53 protein by protein kinase C is abolished by protein kinase CK2
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Articles

Ceramide and glutathione define two independently regulated pathways of cell death initiated by p53 in Molt-4 leukaemia cells

Wissal EL-ASSAAD, Lina KOZHAYA, Sawsan ARAYSI, Shoghag PANJARIAN, Fadi F. BITAR, Elizabeth BAZ, Marwan E. EL-SABBAN, Ghassan S. DBAIBO
Journal: Biochemical Journal
Biochem J (2003) 376 (3): 725–732.
https://doi.org/10.1042/bj20030888
Published: 15 December 2003
...Wissal EL-ASSAAD; Lina KOZHAYA; Sawsan ARAYSI; Shoghag PANJARIAN; Fadi F. BITAR; Elizabeth BAZ; Marwan E. EL-SABBAN; Ghassan S. DBAIBO The tumour suppressor p53 induces cell death by launching several pathways that are either dependent on or independent of gene transcription. Accumulation...
View articletitled, Ceramide and glutathione define two independently regulated pathways of cell death initiated by p53 in Molt-4 leukaemia cells
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Articles

Induced expression of manganese superoxide dismutase by non-toxic concentrations of oxidized low-density lipoprotein (oxLDL) protects against oxLDL-mediated cytotoxicity

Vladimir A. SHATROV, Bernhard BRÜNE
Journal: Biochemical Journal
Biochem J (2003) 374 (2): 505–511.
https://doi.org/10.1042/bj20030420
Published: 01 September 2003
.... 1 To whom correspondence should be addressed (e-mail [email protected] ). 17 3 2003 11 6 2003 25 6 2003 26 6 2003 The Biochemical Society, London ©2003 2003 apoptosis lipoprotein macrophage manganese superoxide dismutase (MnSOD) p53 reactive oxygen species...
View articletitled, Induced expression of manganese superoxide dismutase by non-toxic concentrations of oxidized low-density lipoprotein (oxLDL) protects against oxLDL-mediated cytotoxicity
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Articles

A role for c-Jun N-terminal kinase 1 (JNK1), but not JNK2, in the beta-amyloid-mediated stabilization of protein p53 and induction of the apoptotic cascade in cultured cortical neurons

Marie P. FOGARTY, Eric J. DOWNER, Veronica CAMPBELL
Journal: Biochemical Journal
Biochem J (2003) 371 (3): 789–798.
https://doi.org/10.1042/bj20021660
Published: 01 May 2003
... activity that reached its peak at 1 h and a later activation (at 24 h) of JNK2. The tumour suppressor protein, p53, is a substrate for JNK and can serve as a signalling molecule in apoptosis. In cultured cortical neurons, we found that Aβ increased p53 protein expression and phosphorylation of p53 at Ser...
View articletitled, A role for c-Jun N-terminal kinase 1 (JNK1), but not JNK2, in the beta-amyloid-mediated stabilization of protein p53 and induction of the apoptotic cascade in cultured cortical neurons
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Articles

Iron chelation-induced senescence-like growth arrest in hepatocyte cell lines: association of transforming growth factor β1 (TGF-β1)-mediated p27Kip1 expression

Gyesoon YOON, Hyun-Jung KIM, Young-Sil YOON, Hyeseong CHO, In K. LIM, Jae-Ho LEE
Journal: Biochemical Journal
Biochem J (2002) 366 (2): 613–621.
https://doi.org/10.1042/bj20011445
Published: 01 September 2002
...) antibody, p27 Kip1 induction was completely abolished, indicating that TGF-β1 is the major inducer of p27 Kip1 . Finally, DFO-induced senescence-like arrest was found to be independent of p53, since cell-cycle arrest was still observed with two p53-negative cell lines, Huh7 and Hep3B cells. In conclusion...
View articletitled, Iron chelation-induced senescence-like growth arrest in hepatocyte cell lines: association of transforming growth factor β1 (TGF-β1)-mediated p27Kip1 expression
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