RNF115/BCA2 E3 ubiquitin ligase promotes breast cancer cell proliferation through targeting p21Waf1/Cip1 for ubiquitin-mediated degradation.

Abstract

The E3 ubiquitin ligase RING finger protein 115 (RNF115), also known as breast cancer-associated gene 2 (BCA2), has previously been reported to be overexpressed in estrogen receptor α (ERα)-positive breast tumors and to promote breast cell proliferation; however, its mechanism is unknown. In this study, we demonstrated that silencing of BCA2 by small interfering RNAs (siRNAs) in two ERα-positive breast cancer cell lines, MCF-7 and T47D, decreases cell proliferation and increases the protein levels of the cyclin-dependent kinase inhibitor p21Waf/Cip1. The protein stability of p21 was negatively regulated by BCA2. BCA2 directly interacts with p21 and promotes p21 ubiquitination and proteasomal degradation. Knockdown of p21 partially rescues the cell growth arrest induced by the BCA2 siRNA. These results suggest that BCA2 promotes ERα-positive breast cancer cell proliferation at least partially through downregulating the expression of p21.

• Authors: Zehua Wang, Zhi Nie, Wenlin Chen, Zhongmei Zhou, Qinghua Kong, Arun K Seth, Rong Liu, Ceshi Chen
• Journal: Neoplasia (New York, N.Y.) (Neoplasia) Vol. 15 Issue 9 Pg. 1028-35 (Sep 2013) ISSN: 1476-5586 [Electronic] United States
• PMID: 24027428 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• CDKN1A protein, human
• Cyclin-Dependent Kinase Inhibitor p21
• ESR1 protein, human
• Estrogen Receptor alpha
• RNA, Small Interfering
• Ubiquitin
• RNF115 protein, human
• Ubiquitin-Protein Ligases

Topics

• Breast Neoplasms (metabolism)
• Cell Cycle Checkpoints (genetics)
• Cell Line, Tumor
• Cell Proliferation
• Cyclin-Dependent Kinase Inhibitor p21 (biosynthesis, genetics, metabolism)
• Estrogen Receptor alpha (metabolism)
• Female
• HEK293 Cells
• Humans
• MCF-7 Cells
• RNA Interference
• RNA, Small Interfering
• Ubiquitin (metabolism)
• Ubiquitin-Protein Ligases (genetics, metabolism)
• Ubiquitination