title: BRG1 promotes survival of UV-irradiated melanoma cells by cooperating with MITF to activate the melanoma inhibitor of apoptosis gene.
abstract: Microphthalmia-associated transcription factor (MITF) is a survival factor in melanocytes and melanoma cells. MITF regulates expression of antiapoptotic genes and promotes lineage-specific survival in response to ultraviolet (UV) radiation and to chemotherapeutics. SWI/SNF chromatin-remodeling enzymes interact with MITF to regulate MITF target gene expression. We determined that the catalytic subunit, BRG1, of the SWI/SNF complex protects melanoma cells against UV-induced death. BRG1 prevents apoptosis in UV-irradiated melanoma cells by activating expression of the melanoma inhibitor of apoptosis (ML-IAP). Down-regulation of ML-IAP compromises BRG1-mediated survival of melanoma cells in response to UV radiation. BRG1 regulates ML-IAP expression by cooperating with MITF to promote transcriptionally permissive chromatin structure on the ML-IAP promoter. The alternative catalytic subunit, BRM, and the BRG1-associated factor, BAF180, were found to be dispensable for elevated expression of ML-IAP in melanoma cells. Thus, we illuminate a lineage-specific mechanism by which a specific SWI/SNF subunit, BRG1, modulates the cellular response to DNA damage by regulating an antiapoptotic gene and implicate this subunit of the SWI/SNF complex in mediating the prosurvival function of MITF.
authors.affiliation: Department of Biochemistry and Cancer Biology, University of Toledo College of Medicine, Toledo, OH, USA.
authors.forename: Srinivas V
authors.initials: SV
authors.lastname: Saladi
authors.forename: Philip G
authors.initials: PG
authors.lastname: Wong
authors.forename: Archit R
authors.initials: AR
authors.lastname: Trivedi
authors.forename: Himangi G
authors.initials: HG
authors.lastname: Marathe
authors.forename: Bridget
authors.initials: B
authors.lastname: Keenen
authors.forename: Shweta
authors.initials: S
authors.lastname: Aras
authors.forename: Zi-Qi
authors.initials: ZQ
authors.lastname: Liew
authors.forename: Vijayasaradhi
authors.initials: V
authors.lastname: Setaluri
authors.forename: Ivana L
authors.initials: IL
authors.lastname: de la Serna
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000235:genetics* / Q000378:metabolism; D000818:Animals; D017209:Apoptosis / Q000235:genetics / Q000528:radiation effects; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000528:radiation effects; D002843:Chromatin / Q000378:metabolism; D019610:Cytoprotection / Q000528:radiation effects; D004265:DNA Helicases / Q000378:metabolism*; D004268:DNA-Binding Proteins; D015972:Gene Expression Regulation, Neoplastic / Q000528:radiation effects*; D006657:Histones / Q000378:metabolism; D006801:Humans; D051034:Inhibitor of Apoptosis Proteins / Q000235:genetics* / Q000378:metabolism; D008545:Melanoma / Q000235:genetics* / Q000473:pathology*; D051379:Mice; D051739:Microphthalmia-Associated Transcription Factor / Q000378:metabolism*; D008954:Models, Biological; D009363:Neoplasm Proteins / Q000235:genetics* / Q000378:metabolism; D009687:Nuclear Proteins / Q000378:metabolism*; D011401:Promoter Regions, Genetic / Q000235:genetics; D014157:Transcription Factors / Q000378:metabolism*; D014158:Transcription, Genetic / Q000528:radiation effects; D014466:Ultraviolet Rays
chemical_list: D048868:Adaptor Proteins, Signal Transducing; C419866:BIRC7 protein, human; D002843:Chromatin; D004268:DNA-Binding Proteins; D006657:Histones; D051034:Inhibitor of Apoptosis Proteins; C497234:MITF protein, human; D051739:Microphthalmia-Associated Transcription Factor; D009363:Neoplasm Proteins; D009687:Nuclear Proteins; C102195:PBRM1 protein, human; D014157:Transcription Factors; C084108:SMARCA4 protein, human; D004265:DNA Helicases