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

Journal Article


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.

Authors


  •   Berber, Slavica (external author)
  •   Wood, Mallory (external author)
  •   Llamosas, Estelle (external author)
  •   Thaivalappil, Priya (external author)
  •   Lee, Karen (external author)
  •   Liao, Bing (external author)
  •   Chew, Yee Lian
  •   Rhodes, Aaron (external author)
  •   Yucel, Duygu (external author)
  •   Crossley, Merlin (external author)
  •   Nicholas, Hannah (external author)

Publication Date


  • 2016

Citation


  • Berber, S., Wood, M., Llamosas, E., Thaivalappil, P., Lee, K., Liao, B., Chew, Y., Rhodes, A., Yucel, D., Crossley, M. & Nicholas, H. (2016). Homeodomain-Interacting Protein Kinase (HPK-1) regulates stress responses and ageing in C. elegans. Scientific Reports, 6 19582-1-19582-14.

Scopus Eid


  • 2-s2.0-84955557574

Start Page


  • 19582-1

End Page


  • 19582-14

Volume


  • 6

Place Of Publication


  • United Kingdom

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.

Authors


  •   Berber, Slavica (external author)
  •   Wood, Mallory (external author)
  •   Llamosas, Estelle (external author)
  •   Thaivalappil, Priya (external author)
  •   Lee, Karen (external author)
  •   Liao, Bing (external author)
  •   Chew, Yee Lian
  •   Rhodes, Aaron (external author)
  •   Yucel, Duygu (external author)
  •   Crossley, Merlin (external author)
  •   Nicholas, Hannah (external author)

Publication Date


  • 2016

Citation


  • Berber, S., Wood, M., Llamosas, E., Thaivalappil, P., Lee, K., Liao, B., Chew, Y., Rhodes, A., Yucel, D., Crossley, M. & Nicholas, H. (2016). Homeodomain-Interacting Protein Kinase (HPK-1) regulates stress responses and ageing in C. elegans. Scientific Reports, 6 19582-1-19582-14.

Scopus Eid


  • 2-s2.0-84955557574

Start Page


  • 19582-1

End Page


  • 19582-14

Volume


  • 6

Place Of Publication


  • United Kingdom