BRE/BRCC45 regulates CDC25A stability by recruiting USP7 in response to DNA damage.
BRE/BRCC45 regulates CDC25A stability by recruiting USP7 in response to DNA damage.
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DOI：
10.1038/s41467-018-03020-6
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发表时间：
2018-02-07
影响因子：
16.6
通讯作者：
Sharan SK
中科院分区：
文献类型：
--
作者：
Biswas K;Philip S;Yadav A;Martin BK;Burkett S;Singh V;Babbar A;North SL;Chang S;Sharan SK
BRCA2对于维持基因组的完整性是必不可少的。BRCA2缺陷的原代细胞要么不能存活，要么表现出严重的增殖缺陷。然而，BRCA2缺乏导致了肿瘤的发生。人们认为，Trp53等基因的突变使BRCA2杂合子细胞在失去杂合性时能够克服生长停滞。在这里，我们报告了使用插入突变筛选来确定BRE(脑和生殖器官表达，也称为BRCC45)在BRCA2缺陷小鼠ES细胞生存中的作用。BRE是BRCA1-DNA损伤传感复合体的一部分。BRE过表达导致的细胞活性是由CDC25A磷酸酶调节的，CDC25A磷酸酶是一个关键的细胞周期调节因子和癌基因。我们发现BRE通过招募泛素特异性处理蛋白7(USP7)来促进CDC25A的去泛素化。此外，我们揭示了CDC25A在BRCA介导的肿瘤发生中的作用，这可能对癌症治疗有意义。BRCA2的缺失会导致癌症的形成。在这里，作者使用插入突变的方法，并确定了一个由BRE、USP7和CDC25A组成的多蛋白复合体，它可以支持BRCA2缺陷细胞的生存。
BRCA2 is essential for maintaining genomic integrity. BRCA2-deficient primary cells are either not viable or exhibit severe proliferation defects. Yet, BRCA2 deficiency contributes to tumorigenesis. It is believed that mutations in genes such as TRP53 allow BRCA2 heterozygous cells to overcome growth arrest when they undergo loss of heterozygosity. Here, we report the use of an insertional mutagenesis screen to identify a role for BRE (Brain and Reproductive organ Expressed, also known as BRCC45), known to be a part of the BRCA1-DNA damage sensing complex, in the survival of BRCA2-deficient mouse ES cells. Cell viability by BRE overexpression is mediated by deregulation of CDC25A phosphatase, a key cell cycle regulator and an oncogene. We show that BRE facilitates deubiquitylation of CDC25A by recruiting ubiquitin-specific-processing protease 7 (USP7) in the presence of DNA damage. Additionally, we uncovered the role of CDC25A in BRCA-mediated tumorigenesis, which can have implications in cancer treatment. Loss of BRCA2 leads to cancer formation. Here, the authors use an insertional mutagenesis approach and identify a multiprotein complex consisting of BRE, USP7 and CDC25A that can support the survival of BRCA2-deficient cells.
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影响因子：
8
作者：
Crook, T;Brooks, LA;Gusterson, BA
通讯作者：
Gusterson, BA
影响因子：
11.4
作者：
Cooper, Eric M.;Cutcliffe, Colleen;Cohen, Robert E.
通讯作者：
Cohen, Robert E.
影响因子：
10.5
作者：
Jin, JP;Shirogane, T;Harper, JW
通讯作者：
Harper, JW
影响因子：
16
作者：
Davies, AA;Masson, JY;West, SC
通讯作者：
West, SC
DOI：
10.1073/pnas.87.23.9202
发表时间：
1990-12-01
影响因子：
11.1
作者：
GREZ, M;AKGUN, E;OSTERTAG, W
通讯作者：
OSTERTAG, W