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

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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.

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Authors and Affiliations

  1. 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

    Won Hye Ka, Byung Nyun Chun & Jong Cheol Ahn

  2. Applied Biotechnology Department, Ajou University, 206 Worldcup-ro, Yeongtong-gu, Suwon, 16499, Republic of Korea

    Won Hye Ka & Sang Yo Byun

  3. Department of Systems Biology, College of Life Science and Biotechnology, Yonsei University, 50 Yonsei-ro Seodaemun-gu, Seoul, 03722, Republic of Korea

    Seok Keun Cho

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  1. Won Hye Ka
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Correspondence to Sang Yo Byun or Jong Cheol Ahn.

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Ka, W.H., Cho, S.K., Chun, B.N. et al. The ubiquitin ligase COP1 regulates cell cycle and apoptosis by affecting p53 function in human breast cancer cell lines. Breast Cancer 25, 529–538 (2018). https://doi.org/10.1007/s12282-018-0849-5

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  • DOI: https://doi.org/10.1007/s12282-018-0849-5

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