BRG1 promotes survival of UV-irradiated melanoma cells by cooperating with MITF to activate the melanoma inhibitor of apoptosis gene.
BRG1 promotes survival of UV-irradiated melanoma cells by cooperating with MITF to activate the melanoma inhibitor of apoptosis gene.
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DOI：
10.1111/pcmr.12088
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发表时间：
2013-05
影响因子：
4.3
通讯作者：
de la Serna IL
中科院分区：
文献类型：
--
作者：
Saladi SV;Wong PG;Trivedi AR;Marathe HG;Keenen B;Aras S;Liew ZQ;Setaluri V;de la Serna IL
小眼症相关转录因子（MITF）是黑素细胞和黑素瘤细胞中的存活因子。MITF调节抗凋亡基因的表达，并促进响应紫外线（UV）辐射和化疗药物的谱系特异性存活。SWI/SNF染色质重塑酶与MITF相互作用以调节MITF靶基因表达。我们确定SWI/SNF复合物的催化亚基BRG 1保护黑色素瘤细胞免受UV诱导的死亡。BRG 1通过激活黑色素瘤细胞凋亡抑制剂（ML-IAP）的表达来防止紫外线照射的黑色素瘤细胞的凋亡。ML-IAP的下调损害BRG 1介导的黑色素瘤细胞对UV辐射的存活。BRG 1通过与MITF合作促进ML-IAP启动子上转录允许的染色质结构来调节ML-IAP表达。另一种催化亚基BRM和BRG 1相关因子BAF 180被发现与黑色素瘤细胞中ML-IAP的表达升高有关。因此，我们阐明了一个谱系特异性机制，通过该机制，一个特定的SWI/SNF亚基，BRG 1，通过调节抗凋亡基因来调节细胞对DNA损伤的反应，并暗示SWI/SNF复合物的该亚基介导MITF的促生存功能。
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.
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影响因子：
30.8
作者：
Krauthammer, Michael;Kong, Yong;Ha, Byung Hak;Evans, Perry;Bacchiocchi, Antonella;McCusker, James P.;Cheng, Elaine;Davis, Matthew J.;Goh, Gerald;Choi, Murim;Ariyan, Stephan;Narayan, Deepak;Dutton-Regester, Ken;Capatana, Ana;Holman, Edna C.;Bosenberg, Marcus;Sznol, Mario;Kluger, Harriet M.;Brash, Douglas E.;Stern, David F.;Materin, Miguel A.;Lo, Roger S.;Mane, Shrikant;Ma, Shuangge;Kidd, Kenneth K.;Hayward, Nicholas K.;Lifton, Richard P.;Schlessinger, Joseph;Boggon, Titus J.;Halaban, Ruth
通讯作者：
Halaban, Ruth
影响因子：
3.5
作者：
Lazar, Itay;Perlman, Riki;Kadouri, Luna
通讯作者：
Kadouri, Luna
影响因子：
5.3
作者：
De la Serna, IL;Carlson, KA;Imbalzano, AN
通讯作者：
Imbalzano, AN
影响因子：
10.3
作者：
Lin, H.;Wong, R. P. C.;Li, G.
通讯作者：
Li, G.
影响因子：
3.7
作者：
Kothandapani, Anbarasi;Gopalakrishnan, Kathirvel;Patrick, Steve M.
通讯作者：
Patrick, Steve M.