Oncotarget

Research Papers:

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

Hyun Ho Choi, Liem Phan, Ping-Chieh Chou, Chun-Hui Su, Sai-Ching J. Yeung, Jiun-Sheng Chen and Mong-Hong Lee _

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Oncotarget. 2015; 6:19721-19734. https://doi.org/10.18632/oncotarget.3821

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Abstract

Hyun Ho Choi1,2, Liem Phan1, Ping-Chieh Chou1,3, Chun-Hui Su1, Sai-Ching J. Yeung2,5, Jiun-Sheng Chen1 and Mong-Hong Lee1,2,3,4

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 Program in Genes and Development, The University of Texas Graduate School of Biomedical Sciences at Houston, Houston, TX, USA

5 Department of Cancer Emergency Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX, USA

Correspondence to:

Mong-Hong Lee, email:

Keywords: p27, COP1, ubiquitination, cell cycle

Received: February 18, 2015 Accepted: March 11, 2015 Published: April 14, 2015

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.


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