PMID- 20843328
OWN - NLM
STAT- MEDLINE
DCOM- 20110120
LR  - 20211020
IS  - 1476-4598 (Electronic)
IS  - 1476-4598 (Linking)
VI  - 9
DP  - 2010 Sep 15
TI  - Nuclear export regulation of COP1 by 14-3-3sigma in response to DNA damage.
PG  - 243
LID - 10.1186/1476-4598-9-243 [doi]
AB  - Mammalian constitutive photomorphogenic 1 (COP1) is a p53 E3 ubiquitin ligase 
      involved in regulating p53 protein level. In plants, the dynamic 
      cytoplasm/nucleus distribution of COP1 is important for its function in terms of 
      catalyzing the degradation of target proteins. In mammalian cells, the biological 
      consequence of cytoplasmic distribution of COP1 is not well characterized. Here, 
      we show that DNA damage leads to the redistribution of COP1 to the cytoplasm and 
      that 14-3-3sigma, a p53 target gene product, controls COP1 subcellular localization. 
      Investigation of the underlying mechanism suggests that COP1 S387 phosphorylation 
      is required for COP1 to bind 14-3-3sigma. Significantly, upon DNA damage, 14-3-3sigma 
      binds to phosphorylated COP1 at S387, resulting in COP1's accumulation in the 
      cytoplasm. Cytoplasmic COP1 localization leads to its enhanced ubiquitination. We 
      also show that N-terminal 14-3-3sigma interacts with COP1 and promotes COP1 nuclear 
      export through its NES sequence. Further, we show that COP1 is important in 
      causing p53 nuclear exclusion. Finally, we demonstrate that 14-3-3sigma targets COP1 
      for nuclear export, thereby preventing COP1-mediated p53 nuclear export. 
      Together, these results define a novel, detailed mechanism for the subcellular 
      localization and regulation of COP1 after DNA damage and provide a mechanistic 
      explanation for the notion that 14-3-3sigma's impact on the inhibition of p53 E3 
      ligases is an important step for p53 stabilization after DNA damage.
FAU - Su, Chun-Hui
AU  - Su CH
AD  - Department of Molecular and Cellular Oncology, University of Texas M, D, Anderson 
      Cancer Center, Houston, TX 77030, USA.
FAU - Zhao, Ruiying
AU  - Zhao R
FAU - Velazquez-Torres, Guermarie
AU  - Velazquez-Torres G
FAU - Chen, Jian
AU  - Chen J
FAU - Gully, Christopher
AU  - Gully C
FAU - Yeung, Sai-Ching J
AU  - Yeung SC
FAU - Lee, Mong-Hong
AU  - Lee MH
LA  - eng
GR  - R25TCA57730/PHS 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 - 20100915
PL  - England
TA  - Mol Cancer
JT  - Molecular cancer
JID - 101147698
RN  - 0 (14-3-3 Proteins)
RN  - EC 2.3.2.27 (COP1 protein, human)
RN  - EC 2.3.2.27 (Ubiquitin-Protein Ligases)
SB  - IM
MH  - 14-3-3 Proteins/genetics/*metabolism
MH  - Active Transport, Cell Nucleus/genetics/physiology
MH  - Cell Line
MH  - Cell Nucleus/metabolism
MH  - Cytoplasm/metabolism
MH  - DNA Damage/genetics/*physiology
MH  - Humans
MH  - Immunoblotting
MH  - Immunoprecipitation
MH  - Protein Binding
MH  - Ubiquitin-Protein Ligases/genetics/*metabolism
MH  - Ubiquitination
PMC - PMC2949799
EDAT- 2010/09/17 06:00
MHDA- 2011/01/21 06:00
PMCR- 2010/09/15
CRDT- 2010/09/17 06:00
PHST- 2010/06/28 00:00 [received]
PHST- 2010/09/15 00:00 [accepted]
PHST- 2010/09/17 06:00 [entrez]
PHST- 2010/09/17 06:00 [pubmed]
PHST- 2011/01/21 06:00 [medline]
PHST- 2010/09/15 00:00 [pmc-release]
AID - 1476-4598-9-243 [pii]
AID - 10.1186/1476-4598-9-243 [doi]
PST - epublish
SO  - Mol Cancer. 2010 Sep 15;9:243. doi: 10.1186/1476-4598-9-243.