Blood:RPS15突变型慢性淋巴细胞白血病整体蛋白质合成模式和翻译保真度均发生改变

2018-09-05 MedSci MedSci原创

中心点:CLL的RPS15改变可诱导整体蛋白质合成和翻译保真度发生突变依赖性的变化。RPS15突变可通过蛋白质组学改变破坏细胞蛋白质稳定,主要是影响mRNA转录和细胞代谢。摘要:近期,基因组学研究发现RPS15是慢性淋巴细胞白血病(CLL)侵袭性和耐药性病例中的一种新的驱动基因。RPS15编码核糖体蛋白,其C末端保守,延伸至核糖体的解码中心。Gabriel Bretones等人发现该结构域高度保守

中心点:

CLL的RPS15改变可诱导整体蛋白质合成和翻译保真度发生突变依赖性的变化。

RPS15突变可通过蛋白质组学改变破坏细胞蛋白质稳定,主要是影响mRNA转录和细胞代谢。

摘要:

近期,基因组学研究发现RPS15是慢性淋巴细胞白血病(CLL)侵袭性和耐药性病例中的一种新的驱动基因。RPS15编码核糖体蛋白,其C末端保守,延伸至核糖体的解码中心。

Gabriel Bretones等人发现该结构域高度保守的残基发生突变时会影响两种蛋白质稳定性——增强泛素化介导的降解和细胞增殖率。另一方面,研究人员还发现突变型RPS15可装载到核糖体,以突变特异性方式直接影响整体蛋白质合成和(或)翻译保真性。

定量质谱分析显示,在HEK293T和MEC细胞中,RPS15突变可能会诱导翻译机制发生额外变化,并可在蛋白质组水平发生代谢偏移。

总而言之,本研究表明CLL相关的RPS15突变可能遵循已知的核糖体疾病模式发挥作用,可能由突变型核糖体驱动从低增殖型转变为过度增殖型。在这种情况下,翻译保真度丧失导致的细胞蛋白质稳定改变可被认为是CLL病理的一种新的分子机制。


原始出处:

Gabriel Bretones,et al. Altered patterns of global protein synthesis and translational fidelity in RPS15-mutated chronic lymphocytic leukemia. Blood  2018  :blood-2017-09-804401;  doi: https://doi.org/10.1182/blood-2017-09-804401

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    2018-09-06 kafei

    学习了谢谢

    0

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