Modification of Ran GTPase-activating protein by the small ubiquitin-related modifier SUMO-1 requires Ubc9, an E2-type ubiquitin-conjugating enzyme homologue
Modification of Ran GTPase-activating protein by the small ubiquitin-related modifier SUMO-1 requires Ubc9, an E2-type ubiquitin-conjugating enzyme homologue
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DOI：
10.1074/jbc.273.11.6503
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发表时间：
1998-03-13
影响因子：
4.8
通讯作者：
Anderson, P
中科院分区：
文献类型：
--
作者：
Lee, GW;Melchior, F;Anderson, P
用泛素相关蛋白 SUMO-1 对 Ran GTP 酶激活蛋白 RanGAP1 进行共价修饰，可促进其与 Nup358 的关联，Nup358 是核孔复合物发出的细胞质原纤维的一个组成部分 (1, 2)。在非洲爪蟾卵提取物中，Nup358 存在于与 Ubc9 的复合物中 (3)，Ubc9 是 E2 型泛素缀合蛋白的结构同源物酶（UBC）。在这里，我们发现 Ubc9 的人类同源物 (HsUbc9) 的子集与 RanGAP1 在核膜上共定位，HsUbc9 与重组 SUMO-1 形成硫醇酯缀合物，但不与重组泛素形成硫醇酯缀合物，表明它在功能上与 EB 型 UBC 不同。最后，HsUbc9 是 SUMO-1 修饰 RanGAP1 所必需的。这些结果表明 HsUbc9 是一种新型酶级联的一个组成部分，该级联用 SUMO-1 修饰 RanGAP1 以及可能的其他底物。
Covalent modification of the Ran GTPase-activating protein RanGAP1 with the ubiquitin-related protein SUMO-1 promotes its association with Nup358, a component of the cytoplasmic fibrils emanating from the nuclear pore complex (1, 2), In Xenopus egg extracts, Nup358 can be found in a complex with Ubc9 (3), a structural homologue of the E2-type ubiquitin-conjugating enzymes (UBCs). Here we show that a subset of the human homologue of Ubc9 (HsUbc9) colocalizes with RanGAP1 at the nuclear envelope, HsUbc9 forms thiolester conjugates with recombinant SUMO-1, but not with recombinant ubiquitin, indicating that it is functionally distinct from EB-type UBCs, Finally, HsUbc9 is required for the modification of RanGAP1 by SUMO-1. These results suggest that HsUbc9 is a component of a novel enzymatic cascade that modifies RanGAP1, and possibly other substrates, with SUMO-1.