PMID- 29516369
OWN - NLM
STAT- MEDLINE
DCOM- 20181113
LR  - 20191210
IS  - 1880-4233 (Electronic)
IS  - 1340-6868 (Linking)
VI  - 25
IP  - 5
DP  - 2018 Sep
TI  - The ubiquitin ligase COP1 regulates cell cycle and apoptosis by affecting p53 
      function in human breast cancer cell lines.
PG  - 529-538
LID - 10.1007/s12282-018-0849-5 [doi]
AB  - BACKGROUND: The E3 ubiquitin ligase constitutive photomorphogenic 1 (COP1) 
      mediates cell survival, growth, and development, and interacts with the tumor 
      suppressor protein p53 to induce its ubiquitination and degradation. Recent 
      studies reported that COP1 overexpression is associated with increased cell 
      proliferation, transformation, and disease progression in a variety of cancer 
      types. In this study, we investigated whether COP1 regulates p53-mediated cell 
      cycle arrest and apoptosis in human breast cancer cell lines. METHODS: We 
      downregulated COP1 expression using lentiviral particles expressing short hairpin 
      RNA (shRNA) targeting COP1 and measured the effects of the knockdown in three 
      different breast cancer cell lines. RESULTS: COP1 silencing resulted in p53 
      activation, which induced the expression of p21 and p53-upregulated modulator of 
      apoptosis (PUMA) expression, and reduced the levels of cyclin-dependent kinase 2 
      (CDK2). Notably, knockdown of COP1 was associated with cell cycle arrest during 
      the G(0)/G(1) phase. CONCLUSIONS: The COP1-mediated degradation of p53 regulates 
      cancer cell growth and apoptosis. Our results indicate that COP1 regulates human 
      breast cancer cell proliferation and apoptosis in a p53-dependent manner. These 
      findings suggest that COP1 might be a promising potential target for breast 
      cancer-related gene therapy.
FAU - Ka, Won Hye
AU  - Ka WH
AD  - WJ R&D Center, WOOJUNG BSC, Advanced Institutes of Convergence Technology, 145 
      Gwanggyo-ro, Yeongtong-gu, Suwon-si, Gyeonggi-do, 443-270, Republic of Korea.
AD  - Applied Biotechnology Department, Ajou University, 206 Worldcup-ro, Yeongtong-gu, 
      Suwon, 16499, Republic of Korea.
FAU - Cho, Seok Keun
AU  - Cho SK
AD  - Department of Systems Biology, College of Life Science and Biotechnology, Yonsei 
      University, 50 Yonsei-ro Seodaemun-gu, Seoul, 03722, Republic of Korea.
FAU - Chun, Byung Nyun
AU  - Chun BN
AD  - WJ R&D Center, WOOJUNG BSC, Advanced Institutes of Convergence Technology, 145 
      Gwanggyo-ro, Yeongtong-gu, Suwon-si, Gyeonggi-do, 443-270, Republic of Korea.
FAU - Byun, Sang Yo
AU  - Byun SY
AD  - Applied Biotechnology Department, Ajou University, 206 Worldcup-ro, Yeongtong-gu, 
      Suwon, 16499, Republic of Korea. sybyun@ajou.ac.kr.
FAU - Ahn, Jong Cheol
AU  - Ahn JC
AD  - WJ R&D Center, WOOJUNG BSC, Advanced Institutes of Convergence Technology, 145 
      Gwanggyo-ro, Yeongtong-gu, Suwon-si, Gyeonggi-do, 443-270, Republic of Korea. 
      jcahn@woojungbsc.co.kr.
LA  - eng
PT  - Journal Article
DEP - 20180307
PL  - Japan
TA  - Breast Cancer
JT  - Breast cancer (Tokyo, Japan)
JID - 100888201
RN  - 0 (Apoptosis Regulatory Proteins)
RN  - 0 (BBC3 protein, human)
RN  - 0 (CDKN1A protein, human)
RN  - 0 (Cyclin-Dependent Kinase Inhibitor p21)
RN  - 0 (Proto-Oncogene Proteins)
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)
SB  - IM
MH  - Apoptosis/*physiology
MH  - Apoptosis Regulatory Proteins/genetics
MH  - Breast Neoplasms/genetics/metabolism/*pathology
MH  - Cell Cycle/physiology
MH  - Cell Line, Tumor
MH  - Cell Proliferation/genetics
MH  - Cyclin-Dependent Kinase Inhibitor p21/genetics
MH  - Female
MH  - Gene Expression Regulation, Neoplastic
MH  - Gene Knockdown Techniques
MH  - Humans
MH  - Protein Stability
MH  - Proto-Oncogene Proteins/genetics
MH  - Tumor Suppressor Protein p53/genetics/*metabolism
MH  - Ubiquitin-Protein Ligases/genetics/*metabolism
OTO - NOTNLM
OT  - COP1
OT  - Gene therapy
OT  - RNA silencing
OT  - p53
EDAT- 2018/03/09 06:00
MHDA- 2018/11/14 06:00
CRDT- 2018/03/09 06:00
PHST- 2017/10/17 00:00 [received]
PHST- 2018/02/23 00:00 [accepted]
PHST- 2018/03/09 06:00 [pubmed]
PHST- 2018/11/14 06:00 [medline]
PHST- 2018/03/09 06:00 [entrez]
AID - 10.1007/s12282-018-0849-5 [pii]
AID - 10.1007/s12282-018-0849-5 [doi]
PST - ppublish
SO  - Breast Cancer. 2018 Sep;25(5):529-538. doi: 10.1007/s12282-018-0849-5. Epub 2018 
      Mar 7.