title: 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.affiliation: Department of Biological Sciences, Creative Research Initiative Center for Chromatin Dynamics, Seoul National University, Seoul 151-742, South Korea.
authors.forename: Bogyou
authors.initials: B
authors.lastname: Kim
authors.forename: Hye Jin
authors.initials: HJ
authors.lastname: Nam
authors.forename: Ki Eun
authors.initials: KE
authors.lastname: Pyo
authors.forename: Min Jung
authors.initials: MJ
authors.lastname: Jang
authors.forename: Ik Soo
authors.initials: IS
authors.lastname: Kim
authors.forename: Dongha
authors.initials: D
authors.lastname: Kim
authors.forename: Kyungjin
authors.initials: K
authors.lastname: Boo
authors.forename: Seung Hoon
authors.initials: SH
authors.lastname: Lee
authors.forename: Jong-Bok
authors.initials: JB
authors.lastname: Yoon
authors.forename: Sung Hee
authors.initials: SH
authors.lastname: Baek
authors.forename: Jung Hwa
authors.initials: JH
authors.lastname: Kim
mesh_terms: D001943:Breast Neoplasms / Q000378:metabolism / Q000473:pathology; D045744:Cell Line, Tumor; D044842:Cullin Proteins / Q000235:genetics / Q000378:metabolism*; D005260:Female; D057809:HEK293 Cells; D006801:Humans; D009363:Neoplasm Proteins / Q000378:metabolism*; D009687:Nuclear Proteins / Q000378:metabolism*; D055550:Protein Stability; D012097:Repressor Proteins / Q000378:metabolism*; D044767:Ubiquitin-Protein Ligases / Q000378:metabolism*; D054875:Ubiquitination
chemical_list: C410024:BRMS1 protein, human; C503645:CUL3 protein, human; D044842:Cullin Proteins; D009363:Neoplasm Proteins; D009687:Nuclear Proteins; D012097:Repressor Proteins; C509761:SPOP protein, human; D044767:Ubiquitin-Protein Ligases