USP10 Is a Driver of Ubiquitinated Protein Aggregation and Aggresome Formation to Inhibit Apoptosis.
USP10 Is a Driver of Ubiquitinated Protein Aggregation and Aggresome Formation to Inhibit Apoptosis.
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DOI：
10.1016/j.isci.2018.11.006
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发表时间：
2018-11-30
期刊：
影响因子：
5.8
通讯作者：
Fujii M
中科院分区：
文献类型：
--
作者：
Takahashi M;Kitaura H;Kakita A;Kakihana T;Katsuragi Y;Nameta M;Zhang L;Iwakura Y;Nawa H;Higuchi M;Komatsu M;Fujii M
泛素化蛋白的积累是细胞毒性的，但细胞通过诱导攻击体的形成来消除这些细胞毒性。我们发现，泛素特异性蛋白酶10（USP 10）抑制泛素化蛋白诱导的细胞凋亡，诱导侵略形成。USP 10与泛素受体p62相互作用，这种相互作用增强了p62依赖的泛素化蛋白聚集和侵袭体形成，从而协同抑制细胞凋亡。我们提供的证据表明，USP 10/p62诱导的蛋白质聚集体抑制蛋白酶体活性，增加泛素化蛋白的量，促进侵略形成。USP 10在培养细胞中诱导含有α-突触核蛋白（帕金森病的一种致病蛋白）的侵袭体。在帕金森病脑中，USP 10与疾病相关的攻击体样包涵体Lewy小体中的α-突触核蛋白共定位，表明USP 10通过促进Lewy小体形成抑制α-突触核蛋白诱导的神经毒性。总的来说，这些研究结果表明，USP 10是控制蛋白质聚集相关疾病中蛋白质聚集、攻击性基因组形成和细胞毒性的关键因素。USP 10诱导泛素化蛋白聚集和攻击性基因组形成USP 10通过攻击性基因组形成抑制泛素化蛋白诱导的细胞凋亡USP 10诱导α-突触核蛋白阳性攻击性基因组USP 10与α-突触核蛋白在帕金森病的路易体中共定位分子行为机制;细胞神经科学;细胞生物学
Accumulation of ubiquitinated proteins is cytotoxic, but cells inactivate these cytotoxicities by inducing aggresome formation. We found that ubiquitin-specific protease 10 (USP10) inhibits ubiquitinated protein-induced apoptosis by inducing aggresome formation. USP10 interacted with the ubiquitin receptor p62 and the interaction augmented p62-dependent ubiquitinated protein aggregation and aggresome formation, thereby cooperatively inhibiting apoptosis. We provide evidence that USP10/p62-induced protein aggregates inhibit proteasome activity, which increases the amount of ubiquitinated proteins and promotes aggresome formation. USP10 induced aggresomes containing α-synuclein, a pathogenic protein in Parkinson disease, in cultured cells. In Parkinson disease brains, USP10 was colocalized with α-synuclein in the disease-linked aggresome-like inclusion Lewy bodies, suggesting that USP10 inhibits α-synuclein-induced neurotoxicity by promoting Lewy body formation. Collectively, these findings suggest that USP10 is a critical factor to control protein aggregation, aggresome formation, and cytotoxicity in protein-aggregation-related diseases. USP10 induces ubiquitinated protein aggregation and aggresome formation USP10 inhibits ubiquitinated protein-induced apoptosis by aggresome formation USP10 induces α-synuclein-positive aggresome USP10 is colocalized with α-synuclein in Lewy body in Parkinson disease Molecular Mechanism of Behavior; Cellular Neuroscience; Cell Biology
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影响因子：
64.5
作者：
Kawaguchi, Y;Kovacs, JJ;Yao, TP
通讯作者：
Yao, TP
影响因子：
3.7
作者：
Iwakura Y;Wang R;Inamura N;Araki K;Higashiyama S;Takei N;Nawa H
通讯作者：
Nawa H
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：
5.9
作者：
Higuchi, Masaya;Kawamura, Hiroki;Matsuki, Hideaki;Hara, Toshifumi;Takahashi, Masahiko;Saito, Suguru;Saito, Kousuke;Jiang, Shuying;Naito, Makoto;Kiyonari, Hiroshi;Fujii, Masahiro
通讯作者：
Fujii, Masahiro
影响因子：
8.8
作者：
Lin Z;Yang H;Tan C;Li J;Liu Z;Quan Q;Kong S;Ye J;Gao B;Fang D
通讯作者：
Fang D