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AGING CELL:抑癌基因PTEN如何介导长寿?

2019-02-18 海北 MedSci原创

含PDZ结构域的蛋白质(PDZ蛋白质)可以作为蛋白质-蛋白质相互作用的支架,并且对于各种信号转导过程是至关重要的。然而至今为止,关于PDZ蛋白在机体寿命和衰老中的作用我们仍然知之甚少。

含PDZ结构域的蛋白质(PDZ蛋白质)可以作为蛋白质-蛋白质相互作用的支架,并且对于各种信号转导过程是至关重要的。然而至今为止,关于PDZ蛋白在机体寿命和衰老中的作用我们仍然知之甚少。

最近,研究人员证明了KIN-4,一种含有PDZ结构域的微管相关丝氨酸 - 苏氨酸(MAST)蛋白激酶,是通过结合秀丽隐杆线虫中的PTEN磷酸酶起作用的关键长寿因子。

通过针对PDZ蛋白的靶向遗传筛选,研究人员发现,kin-4是daf-2 /胰岛素/ IGF-1受体突变体的寿命增长所必需的。然后,研究人员还证明神经元是kin-4长寿促进作用的关键组织。

研究人员发现KIN-4的PDZ结构域结合PTEN,这是daf-2突变体寿命延长的关键因素。此外,KIN-4和PTEN之间的相互作用对于延长daf-2突变体的寿命至关重要。

由于秀丽隐杆线虫的寿命调节的许多方面在进化上是保守的,因此MAST家族激酶也可能通过与PTEN的相互作用来调节哺乳动物的衰老和/或年龄相关疾病。


原始出处:

Seon Woo A. An et al. KIN‐4/MAST kinase promotes PTEN‐mediated longevity of Caenorhabditis elegans via binding through a PDZ domain. Aging Cell, 2019; doi: https://doi.org/10.1111/acel.12906


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    2019-03-06 zhouqu_8
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    2019-02-20 xiaogang317
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