Homeodomain-Interacting Protein Kinase (HPK-1) regulates stress responses and ageing in C. elegans
Homeodomain-Interacting Protein Kinase (HPK-1) regulates stress responses and ageing in C. elegans
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DOI：
10.1038/srep19582
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发表时间：
2016-01-21
影响因子：
4.6
通讯作者：
Nicholas, Hannah R.
中科院分区：
文献类型：
--
作者：
Berber, Slavica;Wood, Mallory;Nicholas, Hannah R.
同源结构域相互作用蛋白激酶（HIPK）家族的蛋白质调节哺乳动物系统中的一系列过程，例如DNA损伤反应、细胞增殖和凋亡。秀丽隐杆线虫有一个名为HPK-1的HIPK同源物。以前的研究表明HPK-1与长寿控制有关，并表明这种蛋白质可能以应激依赖的方式进行调节。在这里，我们开始扩大这些观察，通过调查的作用，HPK-1在长寿和热和氧化应激的反应。我们发现HPK-1的水平受热应激的调节，并且HPK-1有助于热或氧化应激后的存活。此外，我们表明，HPK-1是正常寿命所必需的，HPK-1功能的丧失会导致反映过早衰老的生理过程的更快下降。通过微阵列分析，我们发现HPK-1调控的基因包括那些编码在应激反应中发挥重要作用的蛋白质，如I相和II相解毒酶。与长寿保证的作用一致，HPK-1还调节年龄调节基因的表达。最后，我们表明，HPK-1的功能在相同的途径，如α-16调节寿命，并揭示了HPK-1在发展中的新作用。
Proteins of the Homeodomain-Interacting Protein Kinase (HIPK) family regulate an array of processes in mammalian systems, such as the DNA damage response, cellular proliferation and apoptosis. The nematode Caenorhabditis elegans has a single HIPK homologue called HPK-1. Previous studies have implicated HPK-1 in longevity control and suggested that this protein may be regulated in a stress-dependent manner. Here we set out to expand these observations by investigating the role of HPK-1 in longevity and in the response to heat and oxidative stress. We find that levels of HPK-1 are regulated by heat stress, and that HPK-1 contributes to survival following heat or oxidative stress. Additionally, we show that HPK-1 is required for normal longevity, with loss of HPK-1 function leading to a faster decline of physiological processes that reflect premature ageing. Through microarray analysis, we have found that HPK-1-regulated genes include those encoding proteins that serve important functions in stress responses such as Phase I and Phase II detoxification enzymes. Consistent with a role in longevity assurance, HPK-1 also regulates the expression of age-regulated genes. Lastly, we show that HPK-1 functions in the same pathway as DAF-16 to regulate longevity and reveal a new role for HPK-1 in development.