Abstract:
:The regulatory step in ubiquitin (Ub)-mediated protein degradation involves recognition and selection of the target substrate by an E3 Ub-ligase. E3 Ub-ligases evoke sophisticated mechanisms to regulate their activity temporally and spatially, including multiple post-translational modifications, combinatorial E3 Ub-ligase pathways, and subcellular localization. The phosphodegrons of many substrates incorporate the activities of multiple kinases, and ubiquitination only occurs when all necessary phosphorylation signals have been incorporated. In this manner, the precise timing of degradation can be controlled. Another way that the Ub pathway tightly controls the timing of proteolysis is with multiple E3 Ub-ligases acting upon a single target. Lastly, subcellular localization can either promote or prevent degradation by regulating the accessibility of kinases and E3 Ub-ligases. This review highlights recent findings that exemplify these emerging themes in the regulation of E3 Ub-ligase substrate recognition.
journal_name
Oncogenejournal_title
Oncogeneauthors
Ang XL,Wade Harper Jdoi
10.1038/sj.onc.1208614subject
Has Abstractpub_date
2005-04-18 00:00:00pages
2860-70issue
17eissn
0950-9232issn
1476-5594pii
1208614journal_volume
24pub_type
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