Y-box factor YB1 controls p53 apoptotic function
Y-box factor YB1 controls p53 apoptotic function
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DOI：
10.1038/sj.onc.1208998
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发表时间：
2005-12-15
期刊：
影响因子：
8
通讯作者：
Braithwaite, AW
中科院分区：
文献类型：
--
作者：
Homer, C;Knight, DA;Braithwaite, AW
细胞核定位和Y盒结合蛋白YB1的高水平似乎是肿瘤耐药和肿瘤预后的重要指标。YB1还与P53肿瘤抑制蛋白相互作用。在这篇文章中，我们继续探索YB1/P53的相互作用。我们报告YB1的核定位需要转录活性的P53。我们继续展示了核YB1调控P53的功能。我们的数据表明，YB1抑制P53引起细胞死亡和反式激活细胞死亡基因的能力，但不干扰P53反式激活CDKN1A基因的能力，该基因编码细胞周期停滞所需的激酶p21(WAF1/CIP1)，也不干扰MDM2基因。我们还表明，核YB1与P53应激激活后正常乳腺上皮细胞中Bax蛋白水平未能增加有关。总之，这些数据表明，(核)YB1选择性地改变了P53的活性，这可能在一定程度上解释了核YB1与耐药性和不良肿瘤预后的相关性。
Nuclear localization and high levels of the Y-box-binding protein YB1 appear to be important indicators of drug resistance and tumor prognosis. YB1 also interacts with the p53 tumor suppressor protein. In this paper, we have continued to explore YB1/p53 interactions. We report that transcriptionally active p53 is required for nuclear localization of YB1. We go on to show that nuclear YB1 regulates p53 function. Our data demonstrate that YB1 inhibits the ability of p53 to cause cell death and to transactivate cell death genes, but does not interfere with the ability of p53 to transactivate the CDKN1A gene, encoding the kinase p21(WAF1/CIP1) required for cell cycle arrest, nor the MDM2 gene. We also show that nuclear YB1 is associated with a failure to increase the level of the Bax protein in normal mammary epithelial cells after stress activation of p53. Together these data suggest that (nuclear) YB1 selectively alters p53 activity, which may in part provide an explanation for the correlation of nuclear YB1 with drug resistance and poor tumor prognosis.