PMID- 21625211
OWN - NLM
STAT- MEDLINE
DCOM- 20120113
LR  - 20211020
IS  - 1476-5594 (Electronic)
IS  - 0950-9232 (Print)
IS  - 0950-9232 (Linking)
VI  - 30
IP  - 48
DP  - 2011 Dec 1
TI  - COP9 signalosome subunit 6 stabilizes COP1, which functions as an E3 ubiquitin 
      ligase for 14-3-3sigma.
PG  - 4791-801
LID - 10.1038/onc.2011.192 [doi]
AB  - 14-3-3sigma, a gene upregulated by p53 in response to DNA damage, exists as part of a 
      positive-feedback loop, which activates p53 and is a human cancer epithelial 
      marker downregulated in various cancer types. 14-3-3sigma levels are critical for 
      maintaining p53 activity in response to DNA damage and regulating signal 
      mediators such as Akt. In this study, we identify mammalian constitutive 
      photomorphogenic 1 (COP1) as a novel E3 ubiquitin ligase for targeting 14-3-3sigma 
      through proteasomal degradation. We show for the first time that COP9 signalosome 
      subunit 6 (CSN6) associates with COP1 and is involved in 14-3-3sigma 
      ubiquitin-mediated degradation. Mechanistic studies show that CSN6 expression 
      leads to stabilization of COP1 through reducing COP1 self-ubiquitination and 
      decelerating COP1's turnover rate. We also show that CSN6-mediated 14-3-3sigma 
      ubiquitination is compromised when COP1 is knocked down. Thus, CSN6 mediates 
      14-3-3sigma ubiquitination through enhancing COP1 stability. Subsequently, we show 
      that CSN6 causes 14-3-3sigma downregulation, thereby activating Akt and promoting 
      cell survival. Also, CSN6 overexpression leads to increased cell growth, 
      transformation and promotes tumorigenicity. Significantly, 14-3-3sigma expression can 
      correct the abnormalities mediated by CSN6 expression. These data suggest that 
      the CSN6-COP1 axis is involved in 14-3-3sigma degradation, and that deregulation of 
      this axis will promote cell growth and tumorigenicity.
FAU - Choi, H H
AU  - Choi HH
AD  - Department of Molecular and Cellular Oncology, The University of Texas M. D. 
      Anderson Cancer Center, Houston, USA.
FAU - Gully, C
AU  - Gully C
FAU - Su, C-H
AU  - Su CH
FAU - Velazquez-Torres, G
AU  - Velazquez-Torres G
FAU - Chou, P-C
AU  - Chou PC
FAU - Tseng, C
AU  - Tseng C
FAU - Zhao, R
AU  - Zhao R
FAU - Phan, L
AU  - Phan L
FAU - Shaiken, T
AU  - Shaiken T
FAU - Chen, J
AU  - Chen J
FAU - Yeung, S C
AU  - Yeung SC
FAU - Lee, M-H
AU  - Lee MH
LA  - eng
GR  - CA16672/CA/NCI NIH HHS/United States
GR  - R56 CA089266/CA/NCI NIH HHS/United States
GR  - P30 CA016672/CA/NCI NIH HHS/United States
GR  - R25 CA057730/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
DEP - 20110530
PL  - England
TA  - Oncogene
JT  - Oncogene
JID - 8711562
RN  - 0 (14-3-3 Proteins)
RN  - 0 (Biomarkers, Tumor)
RN  - 0 (Multiprotein Complexes)
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)
RN  - EC 3.4.- (Peptide Hydrolases)
RN  - EC 3.4.19.12 (COP9 Signalosome Complex)
SB  - IM
MH  - 14-3-3 Proteins/*metabolism
MH  - Biomarkers, Tumor/*metabolism
MH  - COP9 Signalosome Complex
MH  - Cell Line
MH  - Exonucleases/*metabolism
MH  - Exoribonucleases
MH  - Flow Cytometry
MH  - Humans
MH  - Multiprotein Complexes/*physiology
MH  - Peptide Hydrolases/*physiology
MH  - Polymerase Chain Reaction
MH  - Ubiquitin-Protein Ligases/*metabolism
MH  - Ubiquitination
PMC - PMC3358116
MID - NIHMS377099
EDAT- 2011/06/01 06:00
MHDA- 2012/01/14 06:00
PMCR- 2012/05/22
CRDT- 2011/06/01 06:00
PHST- 2011/06/01 06:00 [entrez]
PHST- 2011/06/01 06:00 [pubmed]
PHST- 2012/01/14 06:00 [medline]
PHST- 2012/05/22 00:00 [pmc-release]
AID - onc2011192 [pii]
AID - 10.1038/onc.2011.192 [doi]
PST - ppublish
SO  - Oncogene. 2011 Dec 1;30(48):4791-801. doi: 10.1038/onc.2011.192. Epub 2011 May 
      30.