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Cell Death & Disease:肾细胞癌中RBCK1能够通过泛素化途径促进p53降解

2019-03-28 AlexYang MedSci原创

肾细胞癌(RCC)大约占据了成年人肿瘤的3%,并且RCC的发生率在世界范围内持续增长。尽管RCC可以在早期阶段通过外科手术来进行治疗,而在晚期患者中5年的生存率却急剧的减少。大多数接受细胞毒性或者靶向药物治疗的RCC患者在治疗期间会在某个时间点产生抗性。因此,鉴定新的RCC治疗靶标是非常必要的。最近,有研究人员发现RANBP2型和包含锌指结构 C3HC4型蛋白 (RBCK1)在人类RCC患者样本中

肾细胞癌(RCC)大约占据了成年人肿瘤的3%,并且RCC的发生率在世界范围内持续增长。尽管RCC可以在早期阶段通过外科手术来进行治疗,而在晚期患者中5年的生存率却急剧的减少。大多数接受细胞毒性或者靶向药物治疗的RCC患者在治疗期间会在某个时间点产生抗性。因此,鉴定新的RCC治疗靶标是非常必要的。

最近,有研究人员发现RANBP2型和包含锌指结构 C3HC4型蛋白 (RBCK1)在人类RCC患者样本中表达增加。多个公共数据库分析阐释了RBCK1表达与RCC患者的不良预后相关。之后,研究人员在RCC细胞中进行了RBCK1缺失试验并发现能够在体内和体外对肾癌细胞的增殖产生巨大影响。RBCK1对细胞增殖的影响可以在P53表达下调的2个表达野生型p53细胞系中抵消。进一步的试验阐释了RBCK1能够通过与p53的直接相互作用来促进p53的多聚泛素化和降解。

最后,研究人员指出,他们的结果表明了通过恢复p53功能,RBCK1可能是RCC治疗的很有前景的靶标。

原始出处:

Sifan Yu, Jie Dai, Meng Ma et al. RBCK1 promotes p53 degradation via ubiquitination in renal cell carcinoma. Cell Death & Disease. 15 Mar 2019.

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    2019-07-12 维他命
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    2019-03-30 zhishijing
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    2019-03-30 cy0328

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