PMID- 21135113
OWN - NLM
STAT- MEDLINE
DCOM- 20110502
LR  - 20211020
IS  - 1538-7445 (Electronic)
IS  - 0008-5472 (Print)
IS  - 0008-5472 (Linking)
VI  - 71
IP  - 3
DP  - 2011 Feb 1
TI  - 14-3-3sigma exerts tumor-suppressor activity mediated by regulation of COP1 
      stability.
PG  - 884-94
LID - 10.1158/0008-5472.CAN-10-2518 [doi]
AB  - Constitutive photomorphogenic 1 (COP1) is a p53-targeting E3 ubiquitin ligase 
      that is downregulated by DNA damage through mechanisms that remain obscure. Here, 
      we report that COP1 is not downregulated following DNA damage in 14-3-3sigma null 
      cells, implicating 14-3-3sigma as a critical regulator in the response of COP1 to DNA 
      damage. We also identified that 14-3-3sigma, a p53 target gene product, interacted 
      with COP1 and controlled COP1 protein stability after DNA damage. Mechanistic 
      studies revealed that 14-3-3sigma enhanced COP1 self-ubiquitination, thereby 
      preventing COP1-mediated p53 ubiquitination, degradation, and transcriptional 
      repression. In addition, we found that COP1 expression promoted cell 
      proliferation, cell transformation, and tumor progression, manifesting its role 
      in cancer promotion, whereas 14-3-3sigma negatively regulated COP1 function and 
      prevented tumor growth in a mouse xenograft model of human cancer. 
      Immunohistochemical analysis of clinical breast and pancreatic cancer specimens 
      demonstrated that COP1 protein levels were inversely correlated with 14-3-3sigma 
      protein levels. Together, our findings define a mechanism for posttranslational 
      regulation of COP1 after DNA damage that can explain the correlation between COP1 
      overexpression and 14-3-3sigma downregulation during tumorigenesis.
FAU - Su, Chun-Hui
AU  - Su CH
AD  - Department of Molecular and Cellular Oncology, The University of Texas M. D. 
      Anderson Cancer Center, Houston, Texas 77030, USA.
FAU - Zhao, Ruiying
AU  - Zhao R
FAU - Zhang, Fanmao
AU  - Zhang F
FAU - Qu, Changju
AU  - Qu C
FAU - Chen, Bo
AU  - Chen B
FAU - Feng, Yin-Hsun
AU  - Feng YH
FAU - Phan, Liem
AU  - Phan L
FAU - Chen, Jian
AU  - Chen J
FAU - Wang, Hua
AU  - Wang H
FAU - Wang, Huamin
AU  - Wang H
FAU - Yeung, Sai-Ching J
AU  - Yeung SC
FAU - Lee, Mong-Hong
AU  - Lee MH
LA  - eng
GR  - P30 CA016672/CA/NCI NIH HHS/United States
GR  - CA16672/CA/NCI NIH HHS/United States
GR  - R56 CA089266/CA/NCI NIH HHS/United States
GR  - R01CA089266/CA/NCI NIH HHS/United States
GR  - R01 CA089266/CA/NCI NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
PT  - Research Support, U.S. Gov't, Non-P.H.S.
DEP - 20101206
PL  - United States
TA  - Cancer Res
JT  - Cancer research
JID - 2984705R
RN  - 0 (14-3-3 Proteins)
RN  - 0 (Biomarkers, Tumor)
RN  - 0 (TP53 protein, human)
RN  - 0 (Tumor Suppressor Protein p53)
RN  - EC 2.3.2.27 (COP1 protein, human)
RN  - EC 2.3.2.27 (Ubiquitin-Protein Ligases)
RN  - EC 3.1.- (Exonucleases)
RN  - EC 3.1.- (Exoribonucleases)
RN  - EC 3.1.- (SFN protein, human)
SB  - IM
MH  - 14-3-3 Proteins/genetics/*metabolism
MH  - Animals
MH  - Biomarkers, Tumor/genetics/*metabolism
MH  - Breast Neoplasms/genetics/metabolism
MH  - Cell Adhesion/physiology
MH  - Cell Growth Processes/physiology
MH  - Cell Line, Tumor
MH  - Colonic Neoplasms/genetics/metabolism
MH  - DNA Damage
MH  - Down-Regulation
MH  - Exonucleases/genetics/*metabolism
MH  - Exoribonucleases
MH  - HCT116 Cells
MH  - Humans
MH  - Mice
MH  - Mice, Nude
MH  - Pancreatic Neoplasms/genetics/metabolism
MH  - Transfection
MH  - Transplantation, Heterologous
MH  - Tumor Suppressor Protein p53/metabolism
MH  - Ubiquitin-Protein Ligases/antagonists & 
      inhibitors/biosynthesis/genetics/*metabolism
MH  - Ubiquitination
PMC - PMC3358120
MID - NIHMS376367
COIS- Disclosure of Potential Conflicts of Interest No potential conflicts of interest 
      were disclosed.
EDAT- 2010/12/08 06:00
MHDA- 2011/05/03 06:00
PMCR- 2012/05/22
CRDT- 2010/12/08 06:00
PHST- 2010/12/08 06:00 [entrez]
PHST- 2010/12/08 06:00 [pubmed]
PHST- 2011/05/03 06:00 [medline]
PHST- 2012/05/22 00:00 [pmc-release]
AID - 0008-5472.CAN-10-2518 [pii]
AID - 10.1158/0008-5472.CAN-10-2518 [doi]
PST - ppublish
SO  - Cancer Res. 2011 Feb 1;71(3):884-94. doi: 10.1158/0008-5472.CAN-10-2518. Epub 
      2010 Dec 6.