... drugs. proteasome SUMO ubiquitin The conjugation of SUMO onto target proteins is mediated by similar machinery as that responsible for the conjugation of ubiquitin and consists of a single dimeric E1 (SAE1/UBA2), a single E2 UBE2I/UBC9 and a limited set of E3s, including SIZ/PIAS proteins...

... demonstrated by numerous disorders (known as ciliopathies) associated with disrupted cilia formation (ciliogenesis). Recent advances describing functional regulators of the primary cilium highlight an emerging role for the ubiquitin–proteasome system (UPS) as a key regulator of ciliogenesis. Although...

...) or familial (fALS) forms. Most fALS-related mutant proteins identified so far are prone to misfolding, and must be degraded in order to protect motoneurons from their toxicity. This process, mediated by molecular chaperones, requires proteasome or autophagic systems. Motoneurons are particularly sensitive...

... on the UPS (ubiquitin–proteasome system) and the ALS (autophagy–lysosome system). In the present paper, we focus on the regulation of the degradation of tau by the UPS and ALS and its relation to tau aggregation. We anticipate that stimulation of these two protein-degradation systems might be a potential...

... is important for its localization at the proteasome, which enhances catalysis. In contrast, a UBL domain in USP4 binds to the catalytic domain and competes with ubiquitin binding. In this process, the UBL domain mimics ubiquitin and partially inhibits catalysis. In USP7, there are five consecutive UBL domains...

...Bernat Crosas; Rosa Farràs; Gemma Marfany; Manuel S. Rodríguez; Timothy M. Thomson The ubiquitin–proteasome field has matured, as is evident from the wide diversity of systems and mechanisms in which it participates and that are the subject of investigation, presented in the Ubiquitin–Proteasome...

...Soyeon Park; Geng Tian; Jeroen Roelofs; Daniel Finley The proteasome is the most complex protease known, with a molecular mass of approx. 3 MDa and 33 distinct subunits. Recent studies reported the discovery of four chaperones that promote the assembly of a 19-subunit subcomplex of the proteasome...

... of ubiquitylated substrates from deubiquitylating enzymes and interference with the action of the proteasome. Consequently, TUBEs behave as ‘ubiquitin traps’ that efficiently capture endogenous ubiquitylated proteins. Interpretations and hypothetical models proposed by different groups to understand...

...Celia R. Berkers; Huib Ovaa The observation that tumour cells are more sensitive to pharmacological inhibition of the proteasome than normal cells has led to the development of the proteasome inhibitor bortezomib. To date, this is the only proteasome inhibitor that has been approved for clinical...

.... Furthermore, endoplasmic reticulum stress and impairment of the ubiquitin–proteasome system probably contribute to neurodegeneration in these diseases. A characteristic feature of AD (Alzheimer's disease) is the abnormal accumulation of Aβ (amyloid β-peptide) in the brain. Evidence shows that the AD...

... conditions the action of many critical cellular factors. The third intracellular proteolysis meeting held by the University La Laguna, Canary Islands, Spain, included speakers working with some of the most important proteolytic systems present in higher eukaryotes, such as the UPS (ubiquitin–proteasome...

...Ulrike Seifert; Elke Krüger Peptide generation by the UPS (ubiquitin–proteasome system) is rate-limiting in MHC class I-restricted antigen presentation in response to virus-induced IFNs (interferons). In this process, the role of IFN-induced rapid remodelling of the UPS is less defined. IFN...

...Luis C. Antón; Eugenia M. Villasevil While it is clear that the proteasome is the major player in degradative proteolysis in the nucleus and cytosol, there is a lack of complete agreement on whether there are alternative proteolytic pathways or activities responsible for a significant degradation...

... by the proteasome after polyubiquitination, we showed that the bulk of c-Fos and Fra-1 can be broken down independently of any prior ubiquitination. Certain conserved structural domains suggest that similar mechanisms may also apply to Fra-2 and FosB. Computer search indicates that certain motifs shared by the Fos...

[email protected] ). 3 7 2007 © The Authors Journal compilation © 2007 Biochemical Society 2007 apoptosis cardiac ischaemia/reperfusion injury ischaemic preconditioning proteasome protein kinase C (PKC) reactive oxygen species Cellular viability is determined by the balance of pro...

... regulatory factors), members of the HECT (homologous to E6-associated protein C-terminus) ubiquitin ligase family, which mediate the proteasomal degradation of Smads and/or receptors. Recently, we have defined a novel interaction between Smads and UCH37 (ubiquitin C-terminal hydrolase 37), a DUB (de...

... 2004 heat-shock protein immunophilin molecular chaperone proteasome retinal degeneration tetratricopeptide repeat LCA (Leber's congenital amaurosis) is inherited in an autosomal recessive manner and is characterized by severely impaired vision or blindness at birth. Mutations in AIPL1...

...O. Coux Despite the central role of the 26 S proteasome in eukaryotic cells, many facets of its structural organization and functioning are still poorly understood. To learn more about the interactions between its different subunits, as well as its possible functional partners in cells, we...

... 17 January 2003 Copyright 2003 Biochemical Society 2003 cancer neurodegeneration protein degradation proteasome ubiquitin Abbreviations used: HECT, h omologous with the E 6-AP C - t erminus; CP, core particle; RP, regulatory particle; CDK, cyclin-dependent kinase; ER...

... Biochemical Society 2003 Mdm2 oligomerization p14ARF p53 proteasome Abbreviations used: LMB, leptomycin B; NES, nuclear-export signal; hMdm2, human Mdm2. 482 Biochemical Society Transactions (2003) Volume 31, part 2 Protecting p53 from degradation S. La ´n1 Department of Surgery...