Regulation of proteasome activity in health and disease.

Regulation of proteasome activity in health and disease.
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DOI:
10.1016/j.bbamcr.2013.08.012
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发表时间:
2014-01
影响因子:
5.1
通讯作者:
Finley, Daniel
Finley, Daniel
中科院分区:
生物学2区
文献类型:
--
作者:
Schmidt, Marion;Finley, Daniel

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The ubiquitin-proteasome system (UPS) is the primary selective degradation system in the nuclei and cytoplasm of eukaryotic cells, required for the turnover of myriad soluble proteins. The hundreds of factors that comprise the UPS include an enzymatic cascade that tags proteins for degradation via the covalent attachment of a poly-ubiquitin chain, and a large multimeric enzyme that degrades ubiquitinated proteins, the proteasome. Protein degradation by the UPS regulates many pathways and is a crucial component of the cellular proteostasis network. Dysfunction of the ubiquitination machinery or the proteolytic activity of the proteasome is associated with numerous human diseases. In this review we discuss the contributions of the proteasome to human pathology, describe mechanisms that regulate the proteolytic capacity of the proteasome, and discuss strategies to modulate proteasome function as a therapeutic approach to ameliorate diseases associated with altered UPS function.
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