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Breast Cancer

, Volume 25, Issue 5, pp 529–538 | Cite as

The ubiquitin ligase COP1 regulates cell cycle and apoptosis by affecting p53 function in human breast cancer cell lines

  • Won Hye Ka
  • Seok Keun Cho
  • Byung Nyun Chun
  • Sang Yo ByunEmail author
  • Jong Cheol AhnEmail author
Original Article

Abstract

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 G0/G1 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.

Keywords

COP1 p53 RNA silencing Gene therapy 

Notes

Compliance with ethical standards

Conflict of interest

The authors declare no conflict of interest.

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Copyright information

© The Japanese Breast Cancer Society 2018

Authors and Affiliations

  1. 1.WJ R&D CenterWOOJUNG BSC, Advanced Institutes of Convergence TechnologySuwon-siRepublic of Korea
  2. 2.Applied Biotechnology DepartmentAjou UniversitySuwonRepublic of Korea
  3. 3.Department of Systems Biology, College of Life Science and BiotechnologyYonsei UniversitySeoulRepublic of Korea

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