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Coordinated regulation of p31Cometand Mad2 expression is required for cellular proliferation

机译:p31Cometand Mad2表达的协调调节是细胞增殖所必需的

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摘要

p31Comet is a well-known interacting partner of the spindle assembly checkpoint (SAC) effector molecule Mad2. At the molecular level it is well established that p31Comet promotes efficient mitotic exit, specifically the metaphase-anaphase transition, by antagonizing Mad2 function. However, there is little knowledge of how p31Comet is regulated or the physiological importance of controlling p31Comet. Here, we show that the Rb-E2F pathway regulates p31Comet expression. In multiple tumor types (including breast and lung) p31Comet expression is increased along with Mad2. Expression of this antagonist-target pair is coordinated in cells and correlated in cancer. Moreover, a narrow range of p31Comet:Mad2 ratios is compatible with cellular viability. Our data suggest that coordinate regulation is important for the outgrowth of oncogenic cell populations. Our findings suggest that altered p31Comet:Mad2 expression ratios may provide new insight into altered SAC function and the generation of chromosomal instability in tumors.
机译:p31Comet是纺锤体装配检查点(SAC)效应分子Mad2的众所周知的相互作用伴侣。在分子水平上,已经确定p31Comet通过拮抗Mad2功能来促进有效的有丝分裂退出,特别是中期到后期的过渡。但是,关于如何调控p31Comet或控制p31Comet的生理重要性的知识很少。在这里,我们显示Rb-E2F途径调节p31Comet表达。在多种肿瘤类型(包括乳腺癌和肺癌)中,p31Comet表达与Mad2一起增加。该拮抗剂-靶对的表达在细胞中协调并在癌症中相关。而且,p31Comet:Mad2比例的窄范围与细胞生存力兼容。我们的数据表明,协调调控对于致癌细胞群的增长非常重要。我们的发现表明,改变的p31Comet:Mad2表达比率可能为改变SAC功能和肿瘤中染色体不稳定性的产生提供新的见解。

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