Breast cancer metastasis suppressor 1 (BRMS1) is destabilized by the Cul3-SPOP E3 ubiquitin ligase complex.

Abstract

Breast cancer metastasis suppressor 1 (BRMS1) suppresses metastasis without affecting primary tumorigenesis. The regulatory mechanism of BRMS1 at the protein level has not been revealed until recently. Here, we found that cullin 3 (Cul3), a component of E3 ubiquitin ligase, is a new binding partner of BRMS1 and the interaction between BRMS1 and Cul3 is mediated by the SPOP adaptor protein. Intriguingly, BRMS1 turns out to be a potent substrate that is ubiquitinated by the Cul3-SPOP complex. Knockdown of SPOP increases the level of BRMS1 protein and represses the expression of BRMS1 repressive target genes such as OPN and uPA in breast cancer cells. These results suggest that the novel regulatory mechanism of BRMS1 by Cul3-SPOP complex is important for breast cancer progression.

• Authors: Bogyou Kim, Hye Jin Nam, Ki Eun Pyo, Min Jung Jang, Ik Soo Kim, Dongha Kim, Kyungjin Boo, Seung Hoon Lee, Jong-Bok Yoon, Sung Hee Baek, Jung Hwa Kim
• Journal: Biochemical and biophysical research communications (Biochem Biophys Res Commun) Vol. 415 Issue 4 Pg. 720-6 (Dec 02 2011) ISSN: 1090-2104 [Electronic] United States
• PMID: 22085717 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2011 Elsevier Inc. All rights reserved.

Chemical References

• BRMS1 protein, human
• CUL3 protein, human
• Cullin Proteins
• Neoplasm Proteins
• Nuclear Proteins
• Repressor Proteins
• SPOP protein, human
• Ubiquitin-Protein Ligases

Topics

• Breast Neoplasms (metabolism, pathology)
• Cell Line, Tumor
• Cullin Proteins (genetics, metabolism)
• Female
• HEK293 Cells
• Humans
• Neoplasm Proteins (metabolism)
• Nuclear Proteins (metabolism)
• Protein Stability
• Repressor Proteins (metabolism)
• Ubiquitin-Protein Ligases (metabolism)
• Ubiquitination