Won Hye Ka1,2, Seok Keun Cho3, Byung Nyun Chun1, Sang Yo Byun4, Jong Cheol Ahn5. 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. 2. Applied Biotechnology Department, Ajou University, 206 Worldcup-ro, Yeongtong-gu, Suwon, 16499, Republic of Korea. 3. Department of Systems Biology, College of Life Science and Biotechnology, Yonsei University, 50 Yonsei-ro Seodaemun-gu, Seoul, 03722, Republic of Korea. 4. Applied Biotechnology Department, Ajou University, 206 Worldcup-ro, Yeongtong-gu, Suwon, 16499, Republic of Korea. sybyun@ajou.ac.kr. 5. 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.
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.
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 humanbreast 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 humanbreast 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.