首页> 外文OA文献 >TP53 exon-6 truncating mutations produce separation of function isoforms with pro-tumorigenic functions
【2h】

TP53 exon-6 truncating mutations produce separation of function isoforms with pro-tumorigenic functions

机译:TP53外显子6截短突变产生具有促肿瘤功能的功能同工型

代理获取
本网站仅为用户提供外文OA文献查询和代理获取服务,本网站没有原文。下单后我们将采用程序或人工为您竭诚获取高质量的原文,但由于OA文献来源多样且变更频繁,仍可能出现获取不到、文献不完整或与标题不符等情况,如果获取不到我们将提供退款服务。请知悉。

摘要

TP53 truncating mutations are common in human tumors and are thought to give rise to p53-null alleles. Here, we show that TP53 exon-6 truncating mutations occur at higher than expected frequencies and produce proteins that lack canonical p53 tumor suppressor activities but promote cancer cell proliferation, survival, and metastasis. Functionally and molecularly, these p53 mutants resemble the naturally occurring alternative p53 splice variant, p53-psi. Accordingly, these mutants can localize to mitochondria where they promote tumor phenotypes by binding and activating the mitochondria inner pore permeability regulator, Cyclophilin D (CypD). Together, our studies reveal that TP53 exon-6 truncating mutations, contrary to current beliefs, act beyond p53 loss to promote tumorigenesis, and could inform the development of strategies to target cancers driven by these prevalent mutations.
机译:TP53截短突变在人类肿瘤中很常见,并且被认为会产生p53-null等位基因。在这里,我们表明TP53外显子6截断突变发生在比预期的频率更高,并产生缺乏规范的p53肿瘤抑制活性,但促进癌细胞增殖,存活和转移的蛋白质。从功能和分子上讲,这些p53突变体类似于天然存在的p53剪接变体p53-psi。因此,这些突变体可以定位于线粒体,在那里它们通过结合和激活线粒体内部孔渗透性调节剂亲环蛋白D(CypD)来促进肿瘤表型。总之,我们的研究表明,与目前的看法相反,TP53外显子6截短突变的作用超出了p53的缺失,从而促进了肿瘤的发生,并可能为靶向由这些普遍突变驱动的癌症的策略提供了信息。

著录项

代理获取

客服邮箱:kefu@zhangqiaokeyan.com

京公网安备:11010802029741号 ICP备案号:京ICP备15016152号-6 六维联合信息科技 (北京) 有限公司©版权所有
  • 客服微信

  • 服务号