Targeting of AMSH to endosomes is required for epidermal growth factor receptor degradation
Targeting of AMSH to endosomes is required for epidermal growth factor receptor degradation
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DOI：
10.1074/jbc.m611635200
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发表时间：
2007-03-30
影响因子：
4.8
通讯作者：
Kirchhausen, Tomas
中科院分区：
文献类型：
--
作者：
Ma, Yu May;Boucrot, Emmanuel;Kirchhausen, Tomas
为了到达溶酶体，下调的受体（例如表皮生长因子受体）必须首先被分选到晚期内涵体（多囊泡体）的内部囊泡中，这是一种泛素依赖性事件，需要运输（ESCRT）蛋白所需的内涵体分选复合物的协调功能。在这里，我们报道了 ESCRT-III 复合体成分 CHMP3 和去泛素化酶 STAM 的 SH3 结构域 (AMSH) 的相关分子在细胞中相互作用。 CHMP3 的显性失活版本专门阻止 AMSH 靶向内体，抑制 EGFR 的降解但不内化，表明内体 AMSH 是多囊泡体途径的功能组成部分。
To reach the lysosomes, down-regulated receptors such as the epidermal growth factor receptor must first be sorted into internal vesicles of late endosomes (multivesicular bodies), a ubiquitin-dependent event that requires the coordinated function of the endosome sorting complex required for transport (ESCRT) proteins. Here we report that CHMP3, an ESCRT-III complex component, and associated molecule of SH3 domain of STAM (AMSH), a deubiquitinating enzyme, interact with each other in cells. A dominant-negative version of CHMP3, which specifically prevents targeting of AMSH to endosomes, inhibits degradation but not internalization of EGFR, suggesting that endosomal AMSH is a functional component of the multivesicular body pathway.