The regulation of NONO by USP11 via deubiquitination is linked to the proliferation of melanoma cells.
The regulation of NONO by USP11 via deubiquitination is linked to the proliferation of melanoma cells.
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USP11 通过去泛素化对 NONO 的调节与黑色素瘤细胞的增殖有关。
DOI：
10.1111/jcmm.16243
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发表时间：
2021-03
影响因子：
5.3
通讯作者：
Ye M
中科院分区：
文献类型：
--
作者：
Feng P;Li L;Dai J;Zhou L;Liu J;Zhao J;Li X;Ling N;Qiu S;Zhang L;Xie T;Chen Y;Donovan MJ;Peng T;Song J;Ye M
泛素特异性蛋白酶11（USP 11）参与DNA修复、细胞凋亡、信号转导和细胞周期的调节。它属于去泛素酶的USP亚家族。尽管先前的研究表明USP 11过表达在黑色素瘤中频繁发现并且与不良预后相关，但是USP 11在黑色素瘤中的潜在分子机制仍然不确定。在这里，我们报告说，USP 11和NONO共定位和相互作用，在黑色素瘤细胞的细胞核。因此，USP 11的敲低降低了NONO水平。然而，USP 11的过表达以剂量依赖性方式增加NONO水平。此外，我们发现USP 11通过去除结合到NONO上的多聚泛素链来保护NONO蛋白免受蛋白酶体介导的降解。在功能上，USP 11通过调节NONO水平介导黑色素瘤细胞增殖，因为USP 11的消融抑制了增殖，这可以通过NONO蛋白的异位表达来挽救。此外，在临床黑色素瘤样本中发现USP 11和NONO浓度之间存在显著正相关。总的来说，这些结果表明USP 11是NONO的一种新的去泛素化酶，并且USP 11-NONO的信号传导轴显著参与黑色素瘤增殖。
Ubiquitin‐specific protease 11 (USP11) has been implicated in the regulation of DNA repair, apoptosis, signal transduction and cell cycle. It belongs to a USP subfamily of deubiquitinases. Although previous research has shown that USP11 overexpression is frequently found in melanoma and is correlated with a poor prognosis, the potential molecular mechanism of USP11 in melanoma remains indefinitive. Here, we report that USP11 and NONO colocalize and interact with each other in the nucleus of melanoma cells. As a result, the knockdown of USP11 decreases NONO levels. Whereas, overexpression of USP11 increases NONO levels in a dose‐dependent manner. Furthermore, we reveal that USP11 protects NONO protein from proteasome‐mediated degradation by removing poly‐ubiquitin chains conjugated onto NONO. Functionally, USP11 mediated melanoma cell proliferation via the regulation of NONO levels because ablation of USP11 inhibits the proliferation which could be rescued by ectopic expression of NONO protein. Moreover, a significant positive correlation between USP11 and NONO concentrations was found in clinical melanoma samples. Collectively, these results demonstrate that USP11 is a new deubiquitinase of NONO and that the signalling axis of USP11‐NONO is significantly involved in melanoma proliferation.
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影响因子：
4.6
作者：
Ho TT;Huang J;Zhou N;Zhang Z;Koirala P;Zhou X;Wu F;Ding X;Mo YY
通讯作者：
Mo YY
影响因子：
10.3
作者：
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影响因子：
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作者：
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通讯作者：
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影响因子：
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作者：
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通讯作者：
Liu, Zhihua