BAG-6 is essential for selective elimination of defective proteasomal substrates.
BAG-6 is essential for selective elimination of defective proteasomal substrates.
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DOI：
10.1083/jcb.200908092
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发表时间：
2010-08-23
期刊：
影响因子：
--
通讯作者：
Kawahara H
中科院分区：
文献类型：
--
作者：
Minami R;Hayakawa A;Kagawa H;Yanagi Y;Yokosawa H;Kawahara H
泛素样蛋白BAG-6通过将细胞与蛋白酶体捆绑在一起，保护细胞免受新合成的错误折叠蛋白的影响。BAG-6/Scythe/BAT3是一种泛素样蛋白，最初被报道是位于人类主要组织相容性复合体中的一个新基因的产物，但其功能机制仍很不清楚。在这里，我们证明了BAG-6参与了哺乳动物细胞中CL1模型缺陷蛋白底物的降解。我们表明，BAG-6不仅对底物的模型降解是必不可少的，而且对新合成的缺陷多肽的泛素介导的代谢也是必不可少的。此外，我们的体内和体外分析表明，BAG-6与嘌呤霉素标记的新生链多肽发生物理相互作用，并调节其蛋白酶体介导的降解。最后，我们发现，BAG-6的敲除导致MHC I类分子在细胞表面的呈现被抑制，这一过程已知受到缺陷核糖体产物的代谢效率的影响。因此，我们认为BAG-6对于泛素介导的新合成缺陷多肽的降解是必要的。
The ubiquitin-like protein BAG-6 protects cells from newly synthesized misfolded proteins by tethering them to the proteasome. BAG-6/Scythe/BAT3 is a ubiquitin-like protein that was originally reported to be the product of a novel gene located within the human major histocompatibility complex, although the mechanisms of its function remain largely obscure. Here, we demonstrate the involvement of BAG-6 in the degradation of a CL1 model defective protein substrate in mammalian cells. We show that BAG-6 is essential for not only model substrate degradation but also the ubiquitin-mediated metabolism of newly synthesized defective polypeptides. Furthermore, our in vivo and in vitro analysis shows that BAG-6 interacts physically with puromycin-labeled nascent chain polypeptides and regulates their proteasome-mediated degradation. Finally, we show that knockdown of BAG-6 results in the suppressed presentation of MHC class I on the cell surface, a procedure known to be affected by the efficiency of metabolism of defective ribosomal products. Therefore, we propose that BAG-6 is necessary for ubiquitin-mediated degradation of newly synthesized defective polypeptides.
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DOI：
10.1083/jcb.143.7.1883
发表时间：
1998-12-28
期刊：
The Journal of cell biology
影响因子：
--
作者：
Johnston JA;Ward CL;Kopito RR
通讯作者：
Kopito RR
影响因子：
16
作者：
Kleijnen, MF;Shih, AH;Howley, PM
通讯作者：
Howley, PM
影响因子：
64.8
作者：
MICHALEK, MT;GRANT, EP;ROCK, KL
通讯作者：
ROCK, KL
影响因子：
11.4
作者：
Gilon, T;Chomsky, O;Kulka, RG
通讯作者：
Kulka, RG
影响因子：
4.8
作者：
Jiang, JH;Ballinger, CA;Patterson, C
通讯作者：
Patterson, C