Proteasomes activate aggresome disassembly and clearance by producing unanchored ubiquitin chains.
Proteasomes activate aggresome disassembly and clearance by producing unanchored ubiquitin chains.
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DOI：
10.1016/j.molcel.2013.08.016
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发表时间：
2013-09-26
期刊：
影响因子：
16
通讯作者：
Yao, Tso-Pang
中科院分区：
文献类型：
--
作者：
Hao, Rui;Nanduri, Priyaanka;Rao, Yanhua;Panichelli, R. Scott;Ito, Akihiro;Yoshida, Minoru;Yao, Tso-Pang
Aberrant protein aggregation is a dominant pathological feature in neurodegenerative diseases. Protein aggregates cannot be processed by the proteasome; instead, they are frequently concentrated to a perinuclear inclusion body, the aggresome, and subsequently removed by autophagy. Paradoxically, proteasomes are also concentrated at aggresomes and other related inclusion bodies prevalent in neurodegenerative disease. Here, we show that proteasomes are crucial components in aggresome clearance. The disassembly and disposal of aggresomes requires a proteasomal deubiquitinating enzyme, Poh1, which cleaves ubiquitinated proteins and releases ubiquitin chains. In Poh1-deficient cells, aggresome clearance is blocked. Remarkably, microinjection of free lysine (K) 63-linked ubiquitin chains restores aggresome degradation. We present evidence that free ubiquitin chains produced by Poh1 bind and activate the deacetylase, HDAC6, which in turn stimulates actinomyosin- and autophagy-dependent aggresome processing. Thus, unanchored ubiquitin chains are key signaling molecules that connect and coordinate the proteasome and autophagy to eliminate toxic protein aggregates.
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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：
64.5
作者：
Zeng W;Sun L;Jiang X;Chen X;Hou F;Adhikari A;Xu M;Chen ZJ
通讯作者：
Chen ZJ
影响因子：
16
作者：
Venkatraman, P;Wetzel, R;Goldberg, AL
通讯作者：
Goldberg, AL
影响因子：
64.8
作者：
Hubbert, C;Guardiola, A;Yao, TP
通讯作者：
Yao, TP
影响因子：
64.5
作者：
Kawaguchi, Y;Kovacs, JJ;Yao, TP
通讯作者：
Yao, TP