title: Breast cancer metastasis suppressor 1 modulates SIRT1-dependent p53 deacetylation through interacting with DBC1.
abstract: Breast cancer metastasis suppressor 1 (BRMS1) is a specific tumor metastasis suppressor implicated in the regulation of chromatin modification and gene transcription. However, the molecular mechanism of BRMS1 remains to be elucidated. Here, we report that DBC1 (deleted in breast cancer 1), is a novel interacting protein of BRMS1. The imperfect leucine zipper motifs of BRMS1 and the N-terminal domain of DBC1 are required for the interaction. DBC1 is identified as an important negative regulator of SIRT1's activity and genotoxic stress response. We demonstrated that BRMS1 is able to interrupt endogenous DBC1-SIRT1 association. Consistently, SIRT1-dependent p53 acetylation under genotoxic stress is also affected by BRMS1. Overall, our results identify BRMS1 as a novel regulator of DBC1-SIRT1 complex and SIRT1-dependent p53 deacetylation.
authors.affiliation: State Key Laboratory of Genetic Engineering, Institute of Genetics, School of Life Sciences, Fudan University Shanghai 200438, P. R. China.
authors.forename: Xueni
authors.initials: X
authors.lastname: Liu
authors.affiliation: State Key Laboratory of Genetic Engineering, Institute of Genetics, School of Life Sciences, Fudan University Shanghai 200438, P. R. China.
authors.forename: Elphire
authors.initials: E
authors.lastname: Ehmed
authors.affiliation: State Key Laboratory of Genetic Engineering, Institute of Genetics, School of Life Sciences, Fudan University Shanghai 200438, P. R. China.
authors.forename: Boyao
authors.initials: B
authors.lastname: Li
authors.affiliation: State Key Laboratory of Genetic Engineering, Institute of Genetics, School of Life Sciences, Fudan University Shanghai 200438, P. R. China.
authors.forename: Jianming
authors.initials: J
authors.lastname: Dou
authors.affiliation: State Key Laboratory of Genetic Engineering, Institute of Genetics, School of Life Sciences, Fudan University Shanghai 200438, P. R. China.
authors.forename: Xiaojing
authors.initials: X
authors.lastname: Qiao
authors.affiliation: State Key Laboratory of Genetic Engineering, Institute of Genetics, School of Life Sciences, Fudan University Shanghai 200438, P. R. China.
authors.forename: Wenyong
authors.initials: W
authors.lastname: Jiang
authors.affiliation: State Key Laboratory of Genetic Engineering, Institute of Genetics, School of Life Sciences, Fudan University Shanghai 200438, P. R. China.
authors.forename: Xi
authors.initials: X
authors.lastname: Yang
authors.affiliation: State Key Laboratory of Genetic Engineering, Institute of Genetics, School of Life Sciences, Fudan University Shanghai 200438, P. R. China.
authors.forename: Shouyi
authors.initials: S
authors.lastname: Qiao
authors.affiliation: State Key Laboratory of Genetic Engineering, Institute of Genetics, School of Life Sciences, Fudan University Shanghai 200438, P. R. China.
authors.forename: Yanhua
authors.initials: Y
authors.lastname: Wu
keywords: BRMS1; DBC1; SIRT1; p53; protein interaction