The Elongin BC complex interacts with the conserved SOCS-box motif present in members of the SOCS, ras, WD-40 repeat, and ankyrin repeat families
The Elongin BC complex interacts with the conserved SOCS-box motif present in members of the SOCS, ras, WD-40 repeat, and ankyrin repeat families
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DOI：
10.1101/gad.12.24.3872
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发表时间：
1998-12-15
影响因子：
10.5
通讯作者：
Conaway, JW
中科院分区：
文献类型：
--
作者：
Kamura, T;Sato, S;Conaway, JW
延伸蛋白BC复合物最初被鉴定为RNA聚合酶II（Pol II）延伸因子延伸蛋白A的正调节因子，随后被鉴定为多蛋白von Hippel-Lindau（VHL）肿瘤抑制复合物的组分，其中它参与肿瘤抑制和缺氧诱导基因的负调节。延伸蛋白B是一种泛素样蛋白，延伸蛋白C是一种Skp 1样蛋白，其结合存在于延伸蛋白A和VHL中的BC盒基序，并且与Skp 1识别的保守F盒基序不同。在这份报告中，我们证明了延伸蛋白BC复合物也结合到一个功能性的BC框中存在的SOCS框，最近在细胞因子信号转导抑制因子-1（SOCS-1）蛋白中发现的序列基序，以及在一个集合中的其他蛋白属于SOCS，ras，WD-40重复，SPRY结构域和锚蛋白重复家族。此外，我们提出的证据表明：（1）Elongin BC复合物是多蛋白SOCS-1复合物的一个组成部分，通过与Jak 2结合并抑制Jak 2激酶来减弱Jak/STAT信号传导，以及（2）通过与SOCS盒相互作用，Elongin BC复合物可以通过抑制SOCS-1蛋白的降解来增加其表达。这些结果表明，延伸蛋白BC是一个多功能的调节复合物，能够控制细胞中的多种途径，通过与在许多不同的蛋白质中发现的短简并序列基序相互作用。
The Elongin BC complex was identified initially as a positive regulator of RNA polymerase II (Pol II) elongation factor Elongin A and subsequently as a component of the multiprotein von Hippel-Lindau (VHL) tumor suppressor complex, in which it participates in both tumor suppression and negative regulation of hypoxia-inducible genes. Elongin B is a ubiquitin-like protein, and Elongin C is a Skp1-like protein that binds to a BC-box motif that is present in both Elongin A and VHL and is distinct from the conserved F-box motif recognized by Skp1. In this report, we demonstrate that the Elongin BC complex also binds to a functional BC box present in the SOCS box, a sequence motif identified recently in the suppressor of cytokine signaling-1 (SOCS-1) protein, as well as in a collection of additional proteins belonging to the SOCS, ras, WD-40 repeat, SPRY domain, and ankyrin repeat families. In addition, we present evidence (1) that the Elongin BC complex is a component of a multiprotein SOCS-1 complex that attenuates Jak/STAT signaling by binding to Jak2 and inhibiting Jak2 kinase, and (2) that by interacting with the SOCS box, the Elongin BC complex can increase expression of the SOCS-1 protein by inhibiting its degradation. These results suggest that Elongin BC is a multifunctional regulatory complex capable of controlling multiple pathways in the cell through interaction with a short degenerate sequence motif found in many different proteins.