TRAF7 sequesters c-Myb to the cytoplasm by stimulating its sumoylation
TRAF7 sequesters c-Myb to the cytoplasm by stimulating its sumoylation
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DOI：
10.1091/mbc.e05-08-0731
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发表时间：
2005-11-01
影响因子：
3.3
通讯作者：
Ishii, S
中科院分区：
文献类型：
--
作者：
Morita, Y;Kanei-Ishii, C;Ishii, S
小泛素相关修饰物 (SUMO) 是翻译后与多种蛋白质缀合的蛋白质。 c-myb 原癌基因产物 (c-Myb) 调节造血细胞的增殖和分化。 PIASy 是唯一已知的 c-Myb SUMO E3 连接酶。在这里，我们报告 TRAF7 与 c-Myb 结合并刺激其 sumoylation。 TRAF7 通过其 WD40 重复序列与 c-Myb 的 DNA 结合域结合。 TRAF7 具有用于自身泛素化的 E3 泛素连接酶活性，但 TRAF7 还刺激 c-Myb 在 Lys-523 和 Lys-499 处的苏酰化，这与 PIASy 诱导的苏酰化所用的位点相同。 TRAF7 抑制野生型 c-Myb 诱导的反式激活，但不抑制 c-Myb 的 sumoylation 位点突变体诱导的反式激活。 M1细胞分化过程中c-myb和TRAF7的表达均下调。内源性 TRAF7 定位于 M1 细胞的细胞质和细胞核。与此一致的是，在 M1 细胞的细胞质中发现了大量的 sumoylated c-Myb，而非 sumoylated c-Myb 主要在细胞核中发现。过表达的 TRAF7 位于 CV-1 细胞的细胞质中，并将 c-Myb 和 SUMO1 隔离在细胞质中，而 PIASy 位于细胞核中。因此，TRAF7 通过苏酰化将 c-Myb 隔离到胞质溶胶中，从而负向调节 c-Myb 活性。
Small ubiquitin-related modifiers (SUMOs) are proteins that are posttranslationally conjugated to diverse proteins. The c-myb proto-oncogene product (c-Myb) regulates proliferation and differentiation of hematopoietic cells. PIASy is the only known SUMO E3 ligase for c-Myb. Here, we report that TRAF7 binds to c-Myb and stimulates its sumoylation. TRAF7 bound to the DNA-binding domain of c-Myb via its WD40 repeats. TRAF7 has an E3 ubiquitin ligase activity for self-ubiquitination, but TRAF7 also stimulated the sumoylation of c-Myb at Lys-523 and Lys-499, which are the same sites as those used for PIASy-induced sumoylation. TRAF7 inhibited trans-activation induced by wild-type c-Myb, but not by the sumoylation site mutant of c-Myb. The expression of both c-myb and TRAF7 was down-regulated during differentiation of M1 cells. Endogenous TRAF7 localized to both the cytoplasm and nucleus of M1 cells. Consistent with this, significant amounts of sumoylated c-Myb were found in the cytoplasm of M1 cells, whereas nonsumoylated c-Myb was found predominantly in the nucleus. Overexpressed TRAF7 was localized in the cytoplasm of CV-1 cells, and sequestered c-Myb and SUMO1 in the cytosol, whereas PIASy was localized in the nucleus. Thus, TRAF7 negatively regulates c-Myb activity by sequestering c-Myb to the cytosol via sumoylation.