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首页> 外文期刊>Oncogene >Expression of an amino-terminal BRCA1 deletion mutant causes a dominant growth inhibition in MCF10A cells
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Expression of an amino-terminal BRCA1 deletion mutant causes a dominant growth inhibition in MCF10A cells

机译:氨基末端BRCA1缺失突变体的表达引起MCF10A细胞显性生长抑制

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Expression of deletion mutants of the breast and ovarian cancer-specific tumor suppressor protein, BRCA1, in the mammary epithelial cell line MCF10A revealed a powerful growth suppressive effect by a mutant that has the amino-terminal 302 amino acids deleted (N-BRCA1). The growth suppression is associated with an increase in apoptosis and amplification in centrosome number. The growth inhibitory effect of N-BRCA1 was not observed in cervical epithelial HeLa cells, suggesting that the phenotypes of BRCA1 mutant proteins differ depending on the cell line being tested. An internal domain, including BRCA1 residues 303–1292, caused the suppression of MCF10A cell growth, and the amino terminus of BRCA1 autoinhibited the growth suppression. Single point mutations that disrupted the amino-terminal RING domain of BRCA1 caused significant suppression of growth in MCF10A cells. These results suggest that the proper function of the RING domain, likely to be ubiquitin ligase function, is important in regulating the growth of the mammary epithelial cell line and in autoregulating the powerful internal growth-inhibiting domain of the BRCA1 tumor suppressor.
机译:乳腺和卵巢癌特异性肿瘤抑制蛋白BRCA1缺失突变体在乳腺上皮细胞系MCF10A中的表达表明,该突变体具有删除了氨基末端302个氨基酸的突变体(N-BRCA1),具有强大的生长抑制作用。生长抑制与凋亡的增加和中心体数目的扩增有关。在宫颈上皮HeLa细胞中未观察到N-BRCA1的生长抑制作用,这表明BRCA1突变蛋白的表型根据所测试的细胞系而有所不同。内部结构域(包括BRCA1残基303–1292)导致MCF10A细胞生长受到抑制,而BRCA1的氨基末端自动抑制了生长抑制。破坏BRCA1氨基末端RING域的单点突变引起MCF10A细胞生长的显着抑制。这些结果表明,RING结构域的适当功能(可能是泛素连接酶功能)对于调节乳腺上皮细胞系的生长以及自动调节BRCA1肿瘤抑制因子强大的内部生长抑制域很重要。

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