The ubiquitin-protein ligase activity of Hdm2 is inhibited by nucleic acids
The ubiquitin-protein ligase activity of Hdm2 is inhibited by nucleic acids
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DOI：
10.1016/s0014-5793(03)01108-6
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发表时间：
2003-11-06
期刊：
影响因子：
3.5
通讯作者：
Scheffner, M
中科院分区：
文献类型：
--
作者：
Linares, LK;Scheffner, M
原癌蛋白Hdm2是环指型泛素蛋白连接酶E3家族的成员。环指结构域被认为介导E3与其同源的泛素结合酶E2的特异性相互作用，从而催化泛素与底物蛋白的共价结合。此外，Hdm2的RING finger结构域参与Hdm2同聚物的形成，并具有以序列特异性方式与RNA结合的能力。在这里，我们报道了与核酸的相互作用干扰了Hdm2/Hdm2复合物的形成和Hdm2的自泛素化。此外，尽管Hdm2与肿瘤抑制因子p53的结合不受核酸的抑制，但Hdm2介导的p53泛素化显著降低。综上所述，这些结果提供了E3活性可以通过与核酸直接相互作用来调节的第一个例子。(C) 2003年欧洲生化学会联合会。Elsevier B.V.版权所有。
The proto-oncoprotein Hdm2 is a member of the RING finger-type family of ubiquitin-protein ligases E3. The RING finger domain is assumed to mediate the specific interaction of an E3 with its cognate ubiquitin-conjugating enzyme E2, which catalyzes the covalent attachment of ubiquitin to substrate proteins. In addition, the RING finger domain of Hdm2 is involved in Hdm2 homooligomer formation and has the capacity to bind to RNA in a sequence-specific manner. Here we report that interaction with nucleic acids interferes with both Hdm2/Hdm2 complex formation and auto-ubiquitination of Hdm2 in vitro. Furthermore, although binding of Hdm2 to the tumor suppressor p53 is not inhibited by nucleic acids, Hdm2-mediated ubiquitination of p53 is significantly decreased. Taken together, these results provide the first example of an E3 whose activity can be regulated by direct interaction with nucleic acids. (C) 2003 Federation of European Biochemical Societies. Published by Elsevier B.V. All rights reserved.