Homeodomain-Interacting Protein Kinase (HPK-1) regulates stress responses and ageing in C. elegans
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.
|ISBN||2045-2322 (Electronic) 2045-2322 (Linking)|
|Authors||Berber, S. ; Wood, M. ; Llamosas, E. ; Thaivalappil, P. ; Lee, K. ; Liao, B. M. ; Chew, Y. L. ; Rhodes, A. ; Yucel, D. ; Crossley, M. ; Nicholas, H. R.;|
|Publisher Name||Scientific Reports|
|URL link to publisher's version||http://www.ncbi.nlm.nih.gov/pubmed/26791749|
|OpenAccess link to author's accepted manuscript version||https://publications.gimr.garvan.org.au/open-access/13969|