Sumoylation of MITF and its related family members TFE3 and TFEB
Sumoylation of MITF and its related family members TFE3 and TFEB
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DOI：
10.1074/jbc.m411757200
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发表时间：
2005-01-07
影响因子：
4.8
通讯作者：
Fisher, DE
中科院分区：
文献类型：
--
作者：
Miller, AJ;Levy, C;Fisher, DE
MITF 及其相关家族成员 TFE3 和 TFEB 彼此异二聚化，识别相同的 DNA 序列，并受到许多相同的翻译后修饰。我们发现这些家族成员中保守的小泛素样修饰剂 (SUMO) 共有位点内的赖氨酸残基受到 SUMO 修饰。这些位点的突变显着影响 MITF 的转录活性，但不会改变二聚化、DNA 结合、稳定性或核定位。诱变将 TRPM1 启动子中 MITF 结合位点的数量从 3 个减少到 1 个，消除了 MITF 突变体之间转录活性的差异。在其他 MITF 靶基因启动子构建体中，野生型和不可SUMO化 MITF 之间的转录活性差异仅在具有多个 MITF 结合位点的启动子中可见。这些数据支持协同控制模型，其中 MITF sumoylation 的功能后果取决于启动子背景。因此，Sumoylation 提供了一种通过影响 MITF 激活的靶基因来改变 MITF 效果的可能机制。
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 nonsumoylatable 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.