USP44 Is an Integral Component of N-CoR that Contributes to Gene Repression by Deubiquitinating Histone H2B.
USP44 Is an Integral Component of N-CoR that Contributes to Gene Repression by Deubiquitinating Histone H2B.
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DOI：
10.1016/j.celrep.2016.10.076
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发表时间：
2016-11-22
期刊：
影响因子：
8.8
通讯作者：
Dent SYR
中科院分区：
文献类型：
--
作者：
Lan X;Atanassov BS;Li W;Zhang Y;Florens L;Mohan RD;Galardy PJ;Washburn MP;Workman JL;Dent SYR
在mES细胞分化过程中，USP 44去泛素化酶的表达减少与H2 Bub 1水平的整体增加相关。然而，USP 44是否直接去泛素化组蛋白H2 B或其活性如何靶向染色质尚不清楚。在这里，我们确定USP 44作为N-CoR复合物的一个组成亚基。N-CoR内的USP 44在体外和体内使H2 B去泛素化，并且USP 44的消融损害N-CoR复合物的抑制活性。ChIP实验证实，USP 44募集降低了N-CoR靶位点的H2 Bub 1水平。此外，USP 44的高表达与乳腺癌细胞系MDA-MB-231中H2 Bub 1水平的降低相关。USP 44或TBL 1XR 1的耗尽损害了体外MDA-MB-231细胞的侵袭力，并导致总体H2 Bub 1水平的增加。总之，我们的研究结果表明，USP 44有助于N-CoR调节基因表达的功能，并且是三阴性乳腺癌细胞有效侵袭所必需的。
Decreased expression of the USP44 deubiquitinase has been associated with global increases in H2Bub1 levels during mES cell differentiation. However, whether USP44 directly deubiquitinates histone H2B or how its activity is targeted to chromatin are not known. Here, we identified USP44 as an integral subunit of the N-CoR complex. USP44 within N-CoR deubiquitinates H2B in vitro and in vivo, and ablation of USP44 impairs the repressive activity of the N-CoR complex. ChIP experiments confirmed that USP44 recruitment reduces H2Bub1 levels at N-CoR target loci. Furthermore, high expression of USP44 correlates with reduced levels of H2Bub1 in the breast cancer cell line MDA-MB-231. Depletion of either USP44 or TBL1XR1 impairs the invasiveness of MDA-MB-231 cells in vitro and causes an increase of global H2Bub1 levels. Together, our findings indicate that USP44 contributes to N-CoR functions in regulating gene expression and is required for efficient invasiveness of triple negative breast cancer cells.
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泛素特异性肽酶42（USP42）的功能可供脱征组蛋白并调节转录活性。
DOI：
10.1074/jbc.m114.589267
发表时间：
2014-12-12
期刊：
The Journal of biological chemistry
影响因子：
--
作者：
Hock AK;Vigneron AM;Vousden KH
通讯作者：
Vousden KH
影响因子：
4.8
作者：
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通讯作者：
D'Andrea, Alan D.
影响因子：
16
作者：
Atanassov BS;Mohan RD;Lan X;Kuang X;Lu Y;Lin K;McIvor E;Li W;Zhang Y;Florens L;Byrum SD;Mackintosh SG;Calhoun-Davis T;Koutelou E;Wang L;Tang DG;Tackett AJ;Washburn MP;Workman JL;Dent SY
通讯作者：
Dent SY
影响因子：
50.3
作者：
Bhaskara S;Knutson SK;Jiang G;Chandrasekharan MB;Wilson AJ;Zheng S;Yenamandra A;Locke K;Yuan JL;Bonine-Summers AR;Wells CE;Kaiser JF;Washington MK;Zhao Z;Wagner FF;Sun ZW;Xia F;Holson EB;Khabele D;Hiebert SW
通讯作者：
Hiebert SW
影响因子：
5.3
作者：
Lang, Guillaume;Bonnet, Jacques;Tora, Laszlo
通讯作者：
Tora, Laszlo