Nat commun:TRIM28能够保护SPOP介导的TRIM24降解并促进前列腺癌恶化

2018-12-14 AlexYang MedSci原创

RIM24是E3泛素连接酶接头SPOP的一个效应底物,并且在SPOP突变的前列腺癌(PCa)中能够保持稳定。然而,TRIM24蛋白在大多数SOOP野生型PCa中是怎样调控的仍旧不清楚。最近,有研究人员报道了TRIM28是TRIM24的关键的上游调控因子。TRIM28能够与TRIM24互作来阻止SPOP介导的TRIM24的泛素化和蛋白降解。更多的是,TRIM28能够促进TRIM24结合到染色质上,并

RIM24是E3泛素连接酶接头SPOP的一个效应底物,并且在SPOP突变的前列腺癌(PCa)中能够保持稳定。然而,TRIM24蛋白在大多数SOOP野生型PCa中是怎样调控的仍旧不清楚。

最近,有研究人员报道了TRIM28是TRIM24的关键的上游调控因子。TRIM28能够与TRIM24互作来阻止SPOP介导的TRIM24的泛素化和蛋白降解。更多的是,TRIM28能够促进TRIM24结合到染色质上,并且与TRIM24相似能够增强AR信号。另外,体外试验和异种种植体内试验中,TRIM28能够促进PCa细胞增殖。重要的是,TRIM28在恶性前列腺癌中表达上调,并且与TRIM24水平的提高和更差的临床结果相关。SPOP突变的PCa中,TRIM24和AR共激活基因能够在人类PCa中能够相似的激活,并且TRIM28的表达较高。

最后,研究人员指出,他们的研究为理解TRIM24蛋白的稳定提供了新的机制,并且建立了TRIM28可以作为一个有希望的治疗靶标的观点。

原始出处:

Ka-wing Fong, Jonathan C. Zhao, Bing Song et al. TRIM28 protects TRIM24 from SPOP-mediated degradation and promotes prostate cancer progression. Nat commun. 27 Nov 2018.

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    2018-12-28 liuli5079
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    2019-09-25 jinweidong
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    2019-01-05 liye789132251

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