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首页> 外文期刊>Cell cycle >A cancer-associated mutation inactivates a region of the high-mobility group protein HMG20b essential for cytokinesis
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A cancer-associated mutation inactivates a region of the high-mobility group protein HMG20b essential for cytokinesis

机译：与癌症相关的突变使细胞分裂所必需的高迁移率族蛋白HMG20b的区域失活

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摘要

Defects in the completion of cell division by cytokinesis have long been proposed to foster carcinogenesis by engendering chromosome instability, but few tumor suppressor mechanisms controlling this process have so far been identified. Here, we identify a carboxyl (C)-terminal region of the high-mobility group protein HMG20b that is essential for cytokinesis, and report that it is inactivated by a cancer-associated mutation. We find that a C-terminal region of HMG20b spanning residues 173-317 is necessary and sufficient not only for its localization to cytokinetic structures, but also for its interaction with the tumor suppressor BRCA2, implicated in the abscission step of cytokinesis. Indeed, expression of this C-terminal HMG20b region suffices to restore cytokinesis in HMG20b-depleted cells. The non-conservative substitution of HMG20b residue Ala247 with Pro, reported in human lung cancer, disrupts these activities of HMG20b, impairing cytokinesis in a trans-dominant manner. Our findings provide fresh insight into the mechanism by which the HMG20b-BRCA2 complex controls mitotic cell division, and implicate heterozygous HMG20b mutations affecting cytokinesis regulation in the genesis of human cancers.
机译：长期以来，人们一直提出通过胞质分裂完成细胞分裂的缺陷通过引起染色体不稳定来促进癌变，但是到目前为止，几乎没有发现控制该过程的肿瘤抑制机制。在这里，我们确定了高迁移率族蛋白HMG20b的羧基（C）末端区域，这对于胞质分裂是必不可少的，并报告说它被癌症相关的突变所灭活。我们发现跨越残基173-317的HMG20b的C末端区域是必要且充分的，不仅对于其定位到细胞动力学结构，而且对于其与肿瘤抑制因子BRCA2的相互作用都涉及胞质分裂的脱落步骤。实际上，该C末端HMG20b区域的表达足以恢复贫乏HMG20b的细胞的胞质分裂。在人类肺癌中，HMG20b残基Ala247被Pro保守取代，从而破坏了HMG20b的这些活性，从而以反式方式破坏了细胞分裂。我们的发现为HMG20b-BRCA2复合物控制有丝分裂细胞分裂的机制提供了新的见解，并暗示杂合的HMG20b突变影响了人类癌症起源中的胞质分裂调控。

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