Ydj1 protects nascent protein kinases from degradation and controls the rate of their maturation
Ydj1 protects nascent protein kinases from degradation and controls the rate of their maturation
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DOI：
10.1128/mcb.00543-08
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发表时间：
2008-07-01
影响因子：
5.3
通讯作者：
Caplan, Avrom J.
中科院分区：
文献类型：
--
作者：
Mandal, Atin K.;Nillegoda, Nadinath B.;Caplan, Avrom J.
Ydj1是酿酒酵母Hsp40分子伴侣，其与Hsp70一起发挥作用以促进多肽折叠。我们确定Ydj1是重要的蛋白激酶的稳定状态水平后，筛选几个伴侣和cochaperones基因缺失突变株。脉冲追踪分析显示，Tpk2激酶的一部分在合成后不久在一个Δ J1突变体中降解，而其余的能够成熟，但与野生型相比动力学降低。Cdc28的成熟也延迟在ESTJ1 Delta突变株。Ydj 1在不同情况下保护新生激酶，例如当Hsp90被格尔德霉素抑制或CDC 37突变时。Ydj1的保护功能部分是由于其内在的伴侣功能，但这是次要的保护作用相比，其与热休克蛋白70的相互作用。SIS1是一种II型Hsp40，不能抑制Ydj1 Delta突变体中激酶积累的缺陷，这表明Ydj1分子伴侣作用具有一定的特异性。然而，嵌合蛋白，包含Ydj1或Sis1的分子伴侣模块的分析表明，Ydj1促进激酶积累独立于其客户端结合特异性。我们的研究结果表明，Ydj1既可以保护新生链降解和控制激酶成熟的速度。
Ydj1 is a Saccharomyces cerevisiae Hsp40 molecular chaperone that functions with Hsp70 to promote polypeptide folding. We identified Ydj1 as being important for maintaining steady-state levels of protein kinases after screening several chaperones and cochaperones in gene deletion mutant strains. Pulse-chase analyses revealed that a portion of Tpk2 kinase was degraded shortly after synthesis in a ydj1 Delta mutant, while the remainder was capable of maturing but with reduced kinetics compared to the wild type. Cdc28 maturation was also delayed in the ydj1 Delta mutant strain. Ydj1 protects nascent kinases in different contexts, such as when Hsp90 is inhibited with geldanamycin or when CDC37 is mutated. The protective function of Ydj1 is due partly to its intrinsic chaperone function, but this is minor compared to the protective effect resulting from its interaction with Hsp70. SIS1, a type II Hsp40, was unable to suppress defects in kinase accumulation in the ydj1 Delta mutant, suggesting some specificity in Ydj1 chaperone action. However, analysis of chimeric proteins that contained the chaperone modules of Ydj1 or Sis1 indicated that Ydj1 promotes kinase accumulation independently of its client-binding specificity. Our results suggest that Ydj1 can both protect nascent chains against degradation and control the rate of kinase maturation.