TY - JOUR
T1 - Sumoylation of MITF and its related family members TFE3 and TFEB
AU - Miller, Arlo J.
AU - Levy, Carmit
AU - Davis, Ian J.
AU - Razin, Ehud
AU - Fisher, David E.
PY - 2005/1/7
Y1 - 2005/1/7
N2 - MITF and its related family members TFE3 and TFEB heterodimerize with each other, recognize the same DNA sequences, and are subject to many of the same post-translational modifications. We show that lysine residues within conserved small ubiquitin-like modifier (SUMO) consensus sites in these family members are subject to SUMO modification. Mutation of these sites significantly affects the transcriptional activity of MITF but does not alter dimerization, DNA binding, stability, or nuclear localization. Mutagenesis reducing the number of MITF binding sites in the promoter of TRPM1 from three to one eliminated the difference in transcriptional activity between the MITF mutants. Among other MITF target gene promoter constructs, differences in transcriptional activity between wild type and non-sumoylatable MITF were only seen in promoters with multiple MITF binding sites. These data support a synergy control model in which the functional consequences of MITF sumoylation depend on promoter context. Sumoylation, thus, provides a possible mechanism for altering the effects of MITF by affecting the target genes that it activates.
AB - MITF and its related family members TFE3 and TFEB heterodimerize with each other, recognize the same DNA sequences, and are subject to many of the same post-translational modifications. We show that lysine residues within conserved small ubiquitin-like modifier (SUMO) consensus sites in these family members are subject to SUMO modification. Mutation of these sites significantly affects the transcriptional activity of MITF but does not alter dimerization, DNA binding, stability, or nuclear localization. Mutagenesis reducing the number of MITF binding sites in the promoter of TRPM1 from three to one eliminated the difference in transcriptional activity between the MITF mutants. Among other MITF target gene promoter constructs, differences in transcriptional activity between wild type and non-sumoylatable MITF were only seen in promoters with multiple MITF binding sites. These data support a synergy control model in which the functional consequences of MITF sumoylation depend on promoter context. Sumoylation, thus, provides a possible mechanism for altering the effects of MITF by affecting the target genes that it activates.
UR - http://www.scopus.com/inward/record.url?scp=12844268574&partnerID=8YFLogxK
U2 - 10.1074/jbc.M411757200
DO - 10.1074/jbc.M411757200
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C2 - 15507434
AN - SCOPUS:12844268574
SN - 0021-9258
VL - 280
SP - 146
EP - 155
JO - Journal of Biological Chemistry
JF - Journal of Biological Chemistry
IS - 1
ER -