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Oncotarget. 2015 Aug 14;6(23):19721-34.

COP1 enhances ubiquitin-mediated degradation of p27Kip1 to promote cancer cell growth.

Choi HH1,2, Phan L1, Chou PC1,3, Su CH1, Yeung SC2,4, Chen JS1, Lee MH1,2,3,5.

Author information

1
Department of Molecular and Cellular Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
2
Institute of Biosciences and Technology, Texas A&M University Health Science Center, Houston, TX, USA.
3
Program in Cancer Biology, The University of Texas Graduate School of Biomedical Sciences at Houston, Houston, TX, USA.
4
Department of Cancer Emergency Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
5
Program in Genes and Development, The University of Texas Graduate School of Biomedical Sciences at Houston, Houston, TX, USA.

Abstract

p27 is a critical CDK inhibitor involved in cell cycle regulation, and its stability is critical for cell proliferation. Constitutive photomorphogenic 1 (COP1) is a RING-containing E3 ubiquitin ligase involved in regulating important target proteins for cell growth, but its biological activity in cell cycle progression is not well characterized. Here, we report that p27Kip1 levels are accumulated in G1 phase, with concurrent reduction of COP1 levels. Mechanistic studies show that COP1 directly interacts with p27 through a VP motif on p27 and functions as an E3 ligase of p27 to accelerate the ubiquitin-mediated degradation of p27. Also, COP1-p27 axis deregulation is involved in tumorigenesis. These findings define a new mechanism for posttranslational regulation of p27 and provide insight into the characteristics of COP1-overexpressing cancers.

KEYWORDS:

COP1; cell cycle; p27; ubiquitination

PMID:
26254224
PMCID:
PMC4637316
DOI:
10.18632/oncotarget.3821
[Indexed for MEDLINE]
Free PMC Article

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