Nuclear receptors (NRs) are cellular proteins, which upon ligand activation, act to exert regulatory control over transcription and subsequent expression. Organized via systemic classification into seven subfamilies, NRs partake in modulating a vast expanse of physiological functions essential for maintenance of life. NRs display particular characteristics towards ubiquitination, the process of addition of specific ubiquitin tags at appropriate locations. Orchestrated through groups of enzymes harboring a diverse array of specialized structural components, the ubiquitination process emphatically alters the fate or downstream effects of NRs. Such influence is especially prominent in transcriptional processes such as promoter clearing for optimization and degradation pathways eliminating or recycling targeted proteins. Ultimately, the ubiquitination of NRs carries significant implications in terms of generating pathological clinical manifestations. Increasing evidence from studies involving patients and disease models suggests a role for ubiquitinated NRs in virtually every organ system. This supports the broad repertoire of roles that NRs play in the body, including modulatory conductors, facilitators, responders to external agents, and critical constituents for pharmacological or biological interventions. This review aims to cover relevant background and mechanisms of NRs and ubiquitination, with a focus towards elucidating subsequent pathophysiology and therapeutics in clinical disorders encompassing such ubiquitinated NRs.
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May 2017
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Image demonstrates the ultrastructural cortical basement membrane changes in SHRSP brain: accumulation of lipofuscin in pericytes. For further details, see article by Screiber et al in this issue (pages 1001–1013). Image kindly provided by Stefanie Schreiber.
Review Article|
May 04 2017
Ubiquitination of nuclear receptors
Jimmy El Hokayem;
Jimmy El Hokayem
*
1Department of Biochemistry and Molecular Biology, University of Miami Miller School of Medicine, Miami, FL, U.S.A.
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Celeste Amadei;
Celeste Amadei
*
1Department of Biochemistry and Molecular Biology, University of Miami Miller School of Medicine, Miami, FL, U.S.A.
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Jean-Pierre Obeid;
Jean-Pierre Obeid
*
1Department of Biochemistry and Molecular Biology, University of Miami Miller School of Medicine, Miami, FL, U.S.A.
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Zafar Nawaz
1Department of Biochemistry and Molecular Biology, University of Miami Miller School of Medicine, Miami, FL, U.S.A.
Correspondence: Zafar Nawaz ([email protected])
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Publisher: Portland Press Ltd
Received:
October 10 2016
Revision Received:
January 26 2017
Accepted:
January 31 2017
Online ISSN: 1470-8736
Print ISSN: 0143-5221
© 2017 The Author(s). published by Portland Press Limited on behalf of the Biochemical Society
2017
Clin Sci (Lond) (2017) 131 (10): 917–934.
Article history
Received:
October 10 2016
Revision Received:
January 26 2017
Accepted:
January 31 2017
Citation
Jimmy El Hokayem, Celeste Amadei, Jean-Pierre Obeid, Zafar Nawaz; Ubiquitination of nuclear receptors. Clin Sci (Lond) 1 May 2017; 131 (10): 917–934. doi: https://doi.org/10.1042/CS20160708
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