Involvement of Rabring7 in EGF receptor degradation as an E3 ligase
Involvement of Rabring7 in EGF receptor degradation as an E3 ligase
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DOI：
10.1016/j.bbrc.2007.04.052
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发表时间：
2007-06-15
影响因子：
3.1
通讯作者：
Sasaki, Takuya
中科院分区：
文献类型：
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作者：
Sakane, Ayuko;Hatakeyama, Shigetsugu;Sasaki, Takuya
Rab7是Rab家族小G蛋白的一员，参与内吞途径的晚期。我们以前发现了一个Rab7靶蛋白Rabring7，它的C端含有一个环指结构域，但Rabring7的确切作用尚不清楚。在这项研究中，我们利用体外泛素化实验证明，重组的E1和E2蛋白使Rabring7具有E3连接酶活性，并且它优先与作为其E2蛋白的Ubc4和Ubc5反应。Rabring7泛素化，但Rab7不泛素化，Ringing7C229S上Cys-229位突变使其E3连接酶活性完全降低。在配体诱导的表皮生长因子受体(EGFR)降解中，Rabring7加速了EGFR的降解，而Rabring7C229S抑制了另一种E3连接酶cCb1的降解。这些结果表明Rabring7通过其E3连接酶活性参与了EGFR的胞内转运。(C)2007 Elsevier Inc.保留所有权利。
Rab7, a member of the Rab family small G proteins, is involved in the late stage of the endocytic pathway. We previously identified a Rab7 target protein, Rabring7, which contains a RING finger domain at its C termini, but the precise role of Rabring7 remains unknown. In this study, we demonstrate using an in vitro ubiquitination assay with recombinant E1 and E2 proteins that Rabring7 has E3 ligase activity and that it preferentially reacts with Ubc4 and Ubc5 as its E2 proteins. Rabring7 ubiquitinated itself but not Rab7, and a mutation at Cys-229 in the RING finger domain (Rabring7C229S) completely diminished its E3 ligase activity. In the ligand-induced degradation of EGF receptor (EGFR), Rabring7 accelerated the degradation of EGFR, whereas Rabring7C229S inhibited the degradation induced by cCb1, another E3 ligase. These results suggest that Rabring7 is involved in the endocytic trafficking of EGFR through its E3 ligase activity. (c) 2007 Elsevier Inc. All rights reserved.