PMID- 26254224
OWN - NLM
STAT- MEDLINE
DCOM- 20160523
LR  - 20191210
IS  - 1949-2553 (Electronic)
IS  - 1949-2553 (Linking)
VI  - 6
IP  - 23
DP  - 2015 Aug 14
TI  - COP1 enhances ubiquitin-mediated degradation of p27Kip1 to promote cancer cell 
      growth.
PG  - 19721-34
AB  - 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.
FAU - Choi, Hyun Ho
AU  - Choi HH
AD  - Department of Molecular and Cellular Oncology, The University of Texas MD 
      Anderson Cancer Center, Houston, TX, USA.
AD  - Institute of Biosciences and Technology, Texas A&M University Health Science 
      Center, Houston, TX, USA.
FAU - Phan, Liem
AU  - Phan L
AD  - Department of Molecular and Cellular Oncology, The University of Texas MD 
      Anderson Cancer Center, Houston, TX, USA.
FAU - Chou, Ping-Chieh
AU  - Chou PC
AD  - Department of Molecular and Cellular Oncology, The University of Texas MD 
      Anderson Cancer Center, Houston, TX, USA.
AD  - Program in Cancer Biology, The University of Texas Graduate School of Biomedical 
      Sciences at Houston, Houston, TX, USA.
FAU - Su, Chun-Hui
AU  - Su CH
AD  - Department of Molecular and Cellular Oncology, The University of Texas MD 
      Anderson Cancer Center, Houston, TX, USA.
FAU - Yeung, Sai-Ching J
AU  - Yeung SC
AD  - Institute of Biosciences and Technology, Texas A&M University Health Science 
      Center, Houston, TX, USA.
AD  - Department of Cancer Emergency Medicine, The University of Texas MD Anderson 
      Cancer Center, Houston, TX, USA.
FAU - Chen, Jiun-Sheng
AU  - Chen JS
AD  - Department of Molecular and Cellular Oncology, The University of Texas MD 
      Anderson Cancer Center, Houston, TX, USA.
FAU - Lee, Mong-Hong
AU  - Lee MH
AD  - Department of Molecular and Cellular Oncology, The University of Texas MD 
      Anderson Cancer Center, Houston, TX, USA.
AD  - Institute of Biosciences and Technology, Texas A&M University Health Science 
      Center, Houston, TX, USA.
AD  - Program in Cancer Biology, The University of Texas Graduate School of Biomedical 
      Sciences at Houston, Houston, TX, USA.
AD  - Program in Genes and Development, The University of Texas Graduate School of 
      Biomedical Sciences at Houston, Houston, TX, USA.
LA  - eng
GR  - P30 CA016672/CA/NCI NIH HHS/United States
GR  - R01 CA089266/CA/NCI NIH HHS/United States
GR  - CA16672/CA/NCI NIH HHS/United States
GR  - R01CA089266/CA/NCI NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, U.S. Gov't, Non-P.H.S.
PL  - United States
TA  - Oncotarget
JT  - Oncotarget
JID - 101532965
RN  - 0 (CDKN1B protein, human)
RN  - 147604-94-2 (Cyclin-Dependent Kinase Inhibitor p27)
RN  - EC 2.3.2.27 (COP1 protein, human)
RN  - EC 2.3.2.27 (Ubiquitin-Protein Ligases)
SB  - IM
MH  - Animals
MH  - Binding Sites
MH  - Cell Cycle
MH  - *Cell Proliferation
MH  - Cyclin-Dependent Kinase Inhibitor p27/genetics/*metabolism
MH  - Gene Expression Regulation, Neoplastic
MH  - HEK293 Cells
MH  - HeLa Cells
MH  - Humans
MH  - Mice, Nude
MH  - Neoplasms/*enzymology/genetics/pathology
MH  - Protein Binding
MH  - Protein Interaction Domains and Motifs
MH  - *Protein Processing, Post-Translational
MH  - *Proteolysis
MH  - Signal Transduction
MH  - Time Factors
MH  - Transfection
MH  - *Tumor Burden
MH  - Ubiquitin-Protein Ligases/genetics/*metabolism
MH  - Ubiquitination
PMC - PMC4637316
OTO - NOTNLM
OT  - COP1
OT  - cell cycle
OT  - p27
OT  - ubiquitination
COIS- CONFLICT OF INTEREST The authors declare that there is no conflict of interest.
EDAT- 2015/08/09 06:00
MHDA- 2016/05/24 06:00
PMCR- 2015/08/14
CRDT- 2015/08/09 06:00
PHST- 2015/02/18 00:00 [received]
PHST- 2015/03/11 00:00 [accepted]
PHST- 2015/08/09 06:00 [entrez]
PHST- 2015/08/09 06:00 [pubmed]
PHST- 2016/05/24 06:00 [medline]
PHST- 2015/08/14 00:00 [pmc-release]
AID - 3821 [pii]
AID - 10.18632/oncotarget.3821 [doi]
PST - ppublish
SO  - Oncotarget. 2015 Aug 14;6(23):19721-34. doi: 10.18632/oncotarget.3821.