SCF-mediated protein degradation and cell cycle control.

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

Oncogene

journal_title

Oncogene

authors

Ang XL,Wade Harper J

doi

10.1038/sj.onc.1208614

subject

Has Abstract

pub_date

2005-04-18 00:00:00

pages

2860-70

issue

17

eissn

0950-9232

issn

1476-5594

pii

1208614

journal_volume

24

pub_type

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