RSUME, a small RWD-containing protein, enhances SUMO conjugation and stabilizes HIF-1α during hypoxia
RSUME, a small RWD-containing protein, enhances SUMO conjugation and stabilizes HIF-1α during hypoxia
复制标题
DOI：
10.1016/j.cell.2007.07.044
复制
发表时间：
2007-10-19
期刊：
影响因子：
64.5
通讯作者：
Arzt, Eduardo
中科院分区：
文献类型：
--
作者：
Carbia-Nagashima, Alberto;Gerez, Juan;Arzt, Eduardo
SUMO与蛋白质的结合参与多种细胞功能的调节。我们已经确定了一种蛋白质，含RWD的SUMO化增强子（RSUME），通过与SUMO缀合酶Ubc 9相互作用增强整体SUMO-1，-2和-3缀合。RSUME增加SUMO-1与Ubc 9的非共价结合，并增强Ubc 9硫酯形成和SUMO聚合。RSUME在体外和培养的细胞中增强IkB的类小泛素化，导致NF-kB转录活性的抑制。RSUME由缺氧诱导，并增强HIF-1 α的类小泛素化，促进其在缺氧期间的稳定和转录活性。RSUME的RWD结构域结构的破坏表明，该结构域对于RSUME作用至关重要。总之，这些发现指出了RSUME在调节类小泛素化中的中心作用，因此，在哺乳动物细胞中有几个关键的调节途径。
SUMO conjugation to proteins is involved in the regulation of diverse cellular functions. We have identified a protein, RWD-containing sumoylation enhancer ( RSUME), that enhances overall SUMO-1, -2, and -3 conjugation by interacting with the SUMO conjugase Ubc9. RSUME increases noncovalent binding of SUMO-1 to Ubc9 and enhances Ubc9 thioester formation and SUMO polymerization. RSUME enhances the sumoylation of IkB in vitro and in cultured cells, leading to an inhibition of NF-kB transcriptional activity. RSUME is induced by hypoxia and enhances the sumoylation of HIF-1 alpha, promoting its stabilization and transcriptional activity during hypoxia. Disruption of the RWD domain structure of RSUME demonstrates that this domain is critical for RSUME action. Together, these findings point to a central role of RSUME in the regulation of sumoylation and, hence, several critical regulatory pathways in mammalian cells.