Format

Send to

Choose Destination
Trends Cell Biol. 2012 Jan;22(1):33-41. doi: 10.1016/j.tcb.2011.10.004. Epub 2011 Dec 9.

Multiple degradation pathways regulate versatile CIP/KIP CDK inhibitors.

Author information

1
Department of Cellular Biology, University of Georgia, Athens, GA 30602, USA. ngs@uga.edu

Abstract

The mammalian CIP/KIP family of cyclin-dependent kinase (CDK) inhibitors (CKIs) comprises three proteins--p21(Cip1/WAF1), p27(Kip1), and p57(Kip2)--that bind and inhibit cyclin-CDK complexes, which are key regulators of the cell cycle. CIP/KIP CKIs have additional independent functions in regulating transcription, apoptosis and actin cytoskeletal dynamics. These divergent functions are performed in distinct cellular compartments and contribute to the seemingly contradictory observation that the CKIs can both suppress and promote cancer. Multiple ubiquitin ligases (E3s) direct the proteasome-mediated degradation of p21, p27 and p57. This review analyzes recent data highlighting our current understanding of how distinct E3 pathways regulate subpopulations of the CKIs to control their diverse functions.

PMID:
22154077
PMCID:
PMC3298816
DOI:
10.1016/j.tcb.2011.10.004
[Indexed for MEDLINE]
Free PMC Article

Supplemental Content

Full text links

Icon for Elsevier Science Icon for PubMed Central
Loading ...
Support Center