Homeodomain-Interacting Protein Kinase (HPK-1) regulates stress responses and ageing in C. elegans

Slavica Berber, Mallory Wood, Estelle Llamosas, Priya Thaivalappil, Karen Lee, Bing Mana Liao, Yee Lian Chew, Aaron Rhodes, Duygu Yucel, Merlin Crossley, Hannah R. Nicholas

Research output: Contribution to journalArticlepeer-review

8 Citations (Scopus)

Abstract

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.

Original languageEnglish
Article number19582
Number of pages14
JournalScientific Reports
Volume6
DOIs
Publication statusPublished - 21 Jan 2016
Externally publishedYes

Keywords

  • Homeodomain-interacting Protein Kinase (HPK-1)
  • Caenorhabditis elegans
  • nematode
  • stress response
  • phase 1
  • phase 2
  • Detoxification enzyme

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