PMID- 25957415
OWN - NLM
STAT- MEDLINE
DCOM- 20160321
LR  - 20191210
IS  - 1949-2553 (Electronic)
IS  - 1949-2553 (Linking)
VI  - 6
IP  - 14
DP  - 2015 May 20
TI  - CSN6 deregulation impairs genome integrity in a COP1-dependent pathway.
PG  - 11779-93
AB  - Understanding genome integrity and DNA damage response are critical to cancer 
      treatment. In this study, we identify CSN6's biological function in regulating 
      genome integrity. Constitutive photomorphogenic 1 (COP1), an E3 ubiquitin ligase 
      regulated by CSN6, is downregulated by DNA damage, but the biological 
      consequences of this phenomenon are poorly understood. p27(Kip1) is a critical 
      CDK inhibitor involved in cell cycle regulation, but its response to DNA damage 
      remains unclear. Here, we report that p27(Kip1) levels are elevated after DNA 
      damage, with concurrent reduction of COP1 levels. Mechanistic studies showed that 
      during DNA damage response COP1's function as an E3 ligase of p27 is compromised, 
      thereby reducing the ubiquitin-mediated degradation of p27(Kip1). Also, COP1 
      overexpression leads to downregulation of p27(Kip1), thereby promoting the 
      expression of mitotic kinase Aurora A. Overexpression of Aurora A correlates with 
      poor survival. These findings provide new insight into CSN6-COP1-p27(Kip1)-Aurora 
      A axis in DNA damage repair and tumorigenesis.
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 - 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 - Fang, Lekun
AU  - Fang L
AD  - Department of Molecular and Cellular Oncology, The University of Texas MD 
      Anderson Cancer Center, Houston, TX, USA.
FAU - Zhang, Jin
AU  - Zhang J
AD  - Key Laboratory of Breast Cancer Prevention and Therapy, Tianjin Medical 
      University, Ministry of Education, Tianjin Medical University Cancer Institute 
      and Hospital, National Clinical Research Center of Cancer, Tianjin, People's 
      Republic of China.
FAU - Yeung, Sai-Ching J
AU  - Yeung SC
AD  - Department of Emergency Medicine, The University of Texas MD Anderson Cancer 
      Center, Houston, TX, USA.
AD  - Departiment of Endocrine Neoplasia and Hormonal Disorders, 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, Non-U.S. Gov't
PT  - Research Support, U.S. Gov't, Non-P.H.S.
PL  - United States
TA  - Oncotarget
JT  - Oncotarget
JID - 101532965
RN  - 0 (Adaptor Proteins, Signal Transducing)
RN  - 0 (COPS6 protein, human)
RN  - EC 2.3.2.27 (COP1 protein, human)
RN  - EC 2.3.2.27 (Ubiquitin-Protein Ligases)
RN  - EC 3.4.19.12 (COP9 Signalosome Complex)
SB  - IM
MH  - Adaptor Proteins, Signal Transducing/*metabolism
MH  - Animals
MH  - COP9 Signalosome Complex
MH  - Carcinogenesis/*genetics
MH  - Cell Line, Tumor
MH  - DNA Damage/genetics
MH  - DNA Repair/genetics
MH  - Fluorescent Antibody Technique
MH  - Heterografts
MH  - Humans
MH  - Immunoblotting
MH  - Mice
MH  - Mice, Nude
MH  - Neoplasms/*genetics/pathology
MH  - Oligonucleotide Array Sequence Analysis
MH  - Signal Transduction/*genetics
MH  - Transfection
MH  - Ubiquitin-Protein Ligases/*metabolism
PMC - PMC4494904
OTO - NOTNLM
OT  - 14-3-3sigma
OT  - COP1
OT  - DNA damage
OT  - p27
OT  - ubiquitination
EDAT- 2015/05/10 06:00
MHDA- 2016/03/22 06:00
PMCR- 2015/05/20
CRDT- 2015/05/10 06:00
PHST- 2014/09/22 00:00 [received]
PHST- 2015/01/17 00:00 [accepted]
PHST- 2015/05/10 06:00 [entrez]
PHST- 2015/05/10 06:00 [pubmed]
PHST- 2016/03/22 06:00 [medline]
PHST- 2015/05/20 00:00 [pmc-release]
AID - 3151 [pii]
AID - 10.18632/oncotarget.3151 [doi]
PST - ppublish
SO  - Oncotarget. 2015 May 20;6(14):11779-93. doi: 10.18632/oncotarget.3151.