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BRG 1 promotes survival of UV ‐irradiated melanoma cells by cooperating with MITF to activate the melanoma inhibitor of apoptosis gene
Author(s) -
Saladi Srinivas V.,
Wong Philip G.,
Trivedi Archit R.,
Marathe Himangi G.,
Keenen Bridget,
Aras Shweta,
Liew ZiQi,
Setaluri Vijayasaradhi,
la Serna Ivana L.
Publication year - 2013
Publication title -
pigment cell and melanoma research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.618
H-Index - 105
eISSN - 1755-148X
pISSN - 1755-1471
DOI - 10.1111/pcmr.12088
Subject(s) - microphthalmia associated transcription factor , melanoma , swi/snf , transcription factor , protein subunit , biology , apoptosis , cancer research , chromatin , microbiology and biotechnology , chemistry , chromatin remodeling , gene , genetics
Summary 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, BRG 1, of the SWI / SNF complex protects melanoma cells against UV ‐induced death. BRG 1 prevents apoptosis in UV ‐irradiated melanoma cells by activating expression of the melanoma inhibitor of apoptosis ( ML ‐ IAP ). Down‐regulation of ML ‐ IAP compromises BRG 1‐mediated survival of melanoma cells in response to UV radiation. BRG 1 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 BRG 1‐associated factor, BAF 180, 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, BRG 1, 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 .