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

• Published in: Breast cancer (Tokyo, Japan) Vol. 25; no. 5; pp. 529 - 538
• Main Authors: Ka, Won Hye, Cho, Seok Keun, Chun, Byung Nyun, Byun, Sang Yo, Ahn, Jong Cheol
• Format: Journal Article
• Language: English
• Published: Tokyo Springer Japan 01-09-2018; Springer
• Subjects: Apoptosis; Breast cancer; Cancer Research; Cell cycle; Health aspects; Ligases; Medicine; Medicine & Public Health; Oncology; Original Article; RNA; Surgery; Surgical Oncology; Tumor proteins; Ubiquitin; COP1; RNA silencing; Gene therapy; p53
• ISSN: 1340-6868; 1880-4233
• DOI: 10.1007/s12282-018-0849-5

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.