USP52 acts as a deubiquitinase and promotes histone chaperone ASF1A stabilization.
USP52 acts as a deubiquitinase and promotes histone chaperone ASF1A stabilization.
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USP52 充当去泛素酶并促进组蛋白伴侣 ASF1A 稳定。
DOI：
10.1038/s41467-018-03588-z
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发表时间：
2018-03-29
影响因子：
16.6
通讯作者：
Shi L
中科院分区：
文献类型：
--
作者：
Yang S;Liu L;Cao C;Song N;Wang Y;Ma S;Zhang Q;Yu N;Ding X;Yang F;Tian S;Zhang K;Sun T;Yang J;Yao Z;Wu S;Shi L
据报道，组蛋白伴侣蛋白ASF1A在多种肿瘤中失调；然而，ASF1A的丰度和功能调控的潜在分子机制尚不清楚。在这里，我们报道ASF1A与USP52存在物理关联，USP52先前被鉴定为伪去泛素酶。有趣的是，我们证明了USP52是一个真正的泛素特异性蛋白酶，USP52促进ASF1A去泛素化和稳定。usp52促进ASF1A稳定，促进染色质组装和促进细胞周期进展。此外，我们发现USP52在乳腺癌中过表达，其表达水平与ASF1A的表达水平相关。此外，我们发现usp52促进的ASF1A稳定性的损害导致乳腺癌细胞生长停滞，并使这些细胞对DNA损伤敏感。我们的实验确定了USP52是一个真正的蛋白质去泛素酶，揭示了USP52在染色质组装中的分子机制，并揭示了USP52在乳腺癌发生中的潜在作用。组蛋白伴侣ASF1A在癌症中经常失调，但其丰度的调控尚不清楚。在这里，作者表明USP52通过去泛素化促进ASF1A的稳定性，而这种稳定性的损害减少了乳腺肿瘤的发生，并赋予了对DNA损伤的敏感性。
Histone chaperone ASF1A has been reported to be dysregulated in multiple tumors; however, the underlying molecular mechanism that how the abundance and function of ASF1A are regulated remains unclear. Here we report that ASF1A is physically associated with USP52, which is previously identified as a pseudo-deubiquitinase. Interestingly, we demonstrate that USP52 is a bona fide ubiquitin-specific protease, and USP52 promotes ASF1A deubiquitination and stabilization. USP52-promoted ASF1A stabilization facilitates chromatin assembly and favors cell cycle progression. Additionally, we find that USP52 is overexpressed in breast carcinomas, and its level of expression correlates with that of ASF1A. Moreover, we reveal that impairment of USP52-promoted ASF1A stabilization results in growth arrest of breast cancer cells and sensitizes these cells to DNA damage. Our experiments identify USP52 as a truly protein deubiquitinase, uncover a molecular mechanism of USP52 in chromatin assembly, and reveal a potential role of USP52 in breast carcinogenesis. Histone chaperone ASF1A is often dysregulated in cancers, however the regulation of its abundance is unclear. Here, the authors show that USP52 promotes ASF1A stability through deubiquitination while impairment of this stability reduces breast tumorigenesis and confers sensitivity to DNA damage.
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影响因子：
64.5
作者：
Goldberg AD;Banaszynski LA;Noh KM;Lewis PW;Elsaesser SJ;Stadler S;Dewell S;Law M;Guo X;Li X;Wen D;Chapgier A;DeKelver RC;Miller JC;Lee YL;Boydston EA;Holmes MC;Gregory PD;Greally JM;Rafii S;Yang C;Scambler PJ;Garrick D;Gibbons RJ;Higgs DR;Cristea IM;Urnov FD;Zheng D;Allis CD
通讯作者：
Allis CD
影响因子：
16
作者：
Faesen, Alex C.;Dirac, Annette M. G.;Sixma, Titia K.
通讯作者：
Sixma, Titia K.
影响因子：
11.4
作者：
Ask, Katrine;Jasencakova, Zuzana;Groth, Anja
通讯作者：
Groth, Anja
ASF1A和ATM调节H3K56介导的细胞周期检查点响应紫外线照射。
影响因子：
14.9
作者：
Battu A;Ray A;Wani AA
通讯作者：
Wani AA
DOI：
10.1038/nrm.2016.159
发表时间：
2017-03
期刊：
Nature reviews. Molecular cell biology
影响因子：
--
作者：
Hammond CM;Strømme CB;Huang H;Patel DJ;Groth A
通讯作者：
Groth A