TRIM11 activates the proteasome and promotes overall protein degradation by regulating USP14.
TRIM11 activates the proteasome and promotes overall protein degradation by regulating USP14.
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DOI：
10.1038/s41467-018-03499-z
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发表时间：
2018-03-26
影响因子：
16.6
通讯作者：
Yang X
中科院分区：
文献类型：
--
作者：
Chen L;Zhu G;Johns EM;Yang X
蛋白酶体是一种复杂的蛋白酶，对蛋白质质量控制和细胞调节至关重要，其功能障碍与癌症和其他疾病有关。然而，控制正常和恶性细胞中蛋白酶体活性的机制仍不清楚。在这里，我们报告了TRIM11增强了异常蛋白和正常调节蛋白的降解，并提高了蛋白质的总降解速度。从机制上讲，TRIM11既能与蛋白酶体结合，又能与USP14结合，USP14是一种去泛素酶，可以过早地从蛋白酶体结合的底物中移除泛素，也可以非催化地抑制蛋白酶体，并排除它们之间的相互作用，从而增加蛋白酶体的活性。TRIM11促进细胞存活，并在热休克时上调。此外，TRIM11是肿瘤生长所必需的，TRIM11的表达增加与临床生存不良相关。这些发现确认TRIM11是蛋白酶体的重要激活剂，定义了一条调节蛋白酶体活性的途径，并揭示了肿瘤细胞获得更高的降解力以支持肿瘤生长的机制。蛋白酶体结合泛素酶USP14在决定蛋白酶体活性和底物特异性方面起着重要作用。在这里，作者表明，TRIM11是哺乳动物三部分基序家族的成员，调节USP14，是蛋白酶体的重要激活剂。
The proteasome is a complex protease critical for protein quality control and cell regulation, and its dysfunction is associated with cancer and other diseases. However, the mechanisms that control proteasome activity in normal and malignant cells remain unclear. Here we report that TRIM11 enhances degradation of aberrant and normal regulatory proteins, and augments overall rate of proteolysis. Mechanistically, TRIM11 binds to both the proteasome and USP14, a deubiquitinase that prematurely removes ubiquitins from proteasome-bound substrates and also noncatalytically inhibits the proteasome, and precludes their association, thereby increasing proteasome activity. TRIM11 promotes cell survival and is upregulated upon heat shock. Moreover, TRIM11 is required for tumor growth, and increased expression of TRIM11 correlates with poor clinical survival. These findings identify TRIM11 as an important activator of the proteasome, define a pathway that adjusts proteasome activity, and reveal a mechanism by which tumor cells acquire higher degradative power to support oncogenic growth. The proteasome-bound ubiquitinase USP14 plays an important role in determining proteasome activity and substrate specificity. Here the authors show that TRIM11, a member of the mammalian tripartite motif family, regulates USP14 and is an important activator of the proteasome.
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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：
16.6
作者：
Finley D
通讯作者：
Finley D
DOI：
10.1006/bbrc.1996.1546
发表时间：
1996-10-14
影响因子：
3.1
作者：
Blagosklonny, MV;Wu, GS;ElDeiry, WS
通讯作者：
ElDeiry, WS
影响因子：
3.5
作者：
Ishikawa, Hideaki;Tachikawa, Hiroyuki;Takahashi, Nobuhiro
通讯作者：
Takahashi, Nobuhiro
DOI：
10.1073/pnas.1510449112
发表时间：
2015-07-14
影响因子：
11.1
作者：
Aufderheide, Antje;Beck, Florian;Foerster, Friedrich
通讯作者：
Foerster, Friedrich