title: Cyclin-dependent kinase-mediated phosphorylation of breast cancer metastasis suppressor 1 (BRMS1) affects cell migration.
abstract: Expression of Breast Cancer Metastasis Suppressor 1 (BRMS1) reduces the incidence of metastasis in many human cancers, without affecting tumorigenesis. BRMS1 carries out this function through several mechanisms, including regulation of gene expression by binding to the mSin3/histone deacetylase (HDAC) transcriptional repressor complex. In the present study, we show that BRMS1 is a novel substrate of Cyclin-Dependent Kinase 2 (CDK2) that is phosphorylated on serine 237 (S237). Although CDKs are known to regulate cell cycle progression, the mutation of BRMS1 on serine 237 did not affect cell cycle progression and proliferation of MDA-MB-231 breast cancer cells; however, their migration was affected. Phosphorylation of BRMS1 does not affect its association with the mSin3/HDAC transcriptional repressor complex or its transcriptional repressor activity. The serine 237 phosphorylation site is immediately proximal to a C-terminal nuclear localization sequence that plays an important role in BRMS1-mediated metastasis suppression but phosphorylation does not control BRMS1 subcellular localization. Our studies demonstrate that CDK-mediated phosphorylation of BRMS1 regulates the migration of tumor cells.
authors.affiliation: a Cell Cycle and Cancer Unit , St Vincent's Institute of Medical Research , Victoria , Australia.|b Department of Medicine , University of Melbourne , Victoria , Australia.
authors.forename: Siti Nur Ain
authors.initials: SN
authors.lastname: Roesley
authors.affiliation: c CSIRO Manufacturing , Victoria , Australia.
authors.forename: Randy
authors.initials: R
authors.lastname: Suryadinata
authors.affiliation: a Cell Cycle and Cancer Unit , St Vincent's Institute of Medical Research , Victoria , Australia.
authors.forename: Emma
authors.initials: E
authors.lastname: Morrish
authors.affiliation: d Baker IDI Heart and Diabetes Institute , Victoria , Australia.
authors.forename: Anthonius Ricardo
authors.initials: AR
authors.lastname: Tan
authors.affiliation: e Metabolic Signalling Laboratory, St Vincent's Institute of Medical Research , Victoria , Australia.
authors.forename: Samah M A
authors.initials: SM
authors.lastname: Issa
authors.affiliation: e Metabolic Signalling Laboratory, St Vincent's Institute of Medical Research , Victoria , Australia.
authors.forename: Jonathan S
authors.initials: JS
authors.lastname: Oakhill
authors.affiliation: b Department of Medicine , University of Melbourne , Victoria , Australia.
authors.forename: Ora
authors.initials: O
authors.lastname: Bernard
authors.affiliation: f Department of Cancer Biology and The University of Kansas Cancer Center , University of Kansas Medical Center , Kansas City , KS , USA.
authors.forename: Danny R
authors.initials: DR
authors.lastname: Welch
authors.affiliation: a Cell Cycle and Cancer Unit , St Vincent's Institute of Medical Research , Victoria , Australia.|b Department of Medicine , University of Melbourne , Victoria , Australia.
authors.forename: Boris
authors.initials: B
authors.lastname: Šarčević
mesh_terms: D001943:Breast Neoplasms / Q000378:metabolism*; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000502:physiology*; D051357:Cyclin-Dependent Kinase 2 / Q000502:physiology*; D005260:Female; D057809:HEK293 Cells; D006801:Humans; D010766:Phosphorylation / Q000502:physiology; D012097:Repressor Proteins / Q000378:metabolism*
chemical_list: C410024:BRMS1 protein, human; D012097:Repressor Proteins; C495894:CDK2 protein, human; D051357:Cyclin-Dependent Kinase 2
keywords: BRMS1; CDK; metastasis suppressor; migration