好斗的
动力蛋白
生物
细胞生物学
HDAC6型
微管
蛋白酶体
蛋白质聚集
未折叠蛋白反应
自噬
动态素
蛋白质稳态
泛素
蛋白质毒性
蛋白质降解
热休克蛋白
应力颗粒
伴侣(临床)
热休克蛋白90
乙酰化
组蛋白脱乙酰基酶
泛素连接酶
生物化学
基因
组蛋白
作者
Yoshiharu Kawaguchi,Jeffery Kovacs,Adam C. McLaurin,Jeffery M. Vance,Akihiro Ito,Tso Pang Yao
出处
期刊:Cell
[Elsevier]
日期:2003-12-01
卷期号:115 (6): 727-738
被引量:1330
标识
DOI:10.1016/s0092-8674(03)00939-5
摘要
The efficient clearance of cytotoxic misfolded protein aggregates is critical for cell survival. Misfolded protein aggregates are transported and removed from the cytoplasm by dynein motors via the microtubule network to a novel organelle termed the aggresome where they are processed. However, the means by which dynein motors recognize misfolded protein cargo, and the cellular factors that regulate aggresome formation, remain unknown. We have discovered that HDAC6, a microtubule-associated deacetylase, is a component of the aggresome. We demonstrate that HDAC6 has the capacity to bind both polyubiquitinated misfolded proteins and dynein motors, thereby acting to recruit misfolded protein cargo to dynein motors for transport to aggresomes. Indeed, cells deficient in HDAC6 fail to clear misfolded protein aggregates from the cytoplasm, cannot form aggresomes properly, and are hypersensitive to the accumulation of misfolded proteins. These findings identify HDAC6 as a crucial player in the cellular management of misfolded protein-induced stress.
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