COP1 enhances ubiquitin-mediated degradation of p27Kip1 to promote cancer cell growth.
Oncotarget
; 6(23): 19721-34, 2015 Aug 14.
Article
in En
| MEDLINE
| ID: mdl-26254224
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.
Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Protein Processing, Post-Translational
/
Ubiquitin-Protein Ligases
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Tumor Burden
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Cell Proliferation
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Cyclin-Dependent Kinase Inhibitor p27
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Proteolysis
/
Neoplasms
Limits:
Animals
/
Humans
Language:
En
Journal:
Oncotarget
Year:
2015
Document type:
Article
Affiliation country:
United States