title: Homeodomain-Interacting Protein Kinase (HPK-1) regulates stress responses and ageing in C. elegans.
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.affiliation: School of Molecular Bioscience, University of Sydney, Sydney, Australia.
authors.forename: Slavica
authors.initials: S
authors.lastname: Berber
authors.affiliation: School of Molecular Bioscience, University of Sydney, Sydney, Australia.
authors.forename: Mallory
authors.initials: M
authors.lastname: Wood
authors.affiliation: School of Molecular Bioscience, University of Sydney, Sydney, Australia.
authors.forename: Estelle
authors.initials: E
authors.lastname: Llamosas
authors.affiliation: School of Molecular Bioscience, University of Sydney, Sydney, Australia.
authors.forename: Priya
authors.initials: P
authors.lastname: Thaivalappil
authors.affiliation: School of Molecular Bioscience, University of Sydney, Sydney, Australia.
authors.forename: Karen
authors.initials: K
authors.lastname: Lee
authors.affiliation: School of Molecular Bioscience, University of Sydney, Sydney, Australia.
authors.forename: Bing Mana
authors.initials: BM
authors.lastname: Liao
authors.affiliation: School of Molecular Bioscience, University of Sydney, Sydney, Australia.
authors.forename: Yee Lian
authors.initials: YL
authors.lastname: Chew
authors.affiliation: School of Molecular Bioscience, University of Sydney, Sydney, Australia.
authors.forename: Aaron
authors.initials: A
authors.lastname: Rhodes
authors.affiliation: School of Molecular Bioscience, University of Sydney, Sydney, Australia.
authors.forename: Duygu
authors.initials: D
authors.lastname: Yucel
authors.affiliation: School of Biotechnology and Biomolecular Sciences, University of New South Wales, Kensington, Australia.
authors.forename: Merlin
authors.initials: M
authors.lastname: Crossley
authors.affiliation: School of Molecular Bioscience, University of Sydney, Sydney, Australia.
authors.forename: Hannah R
authors.initials: HR
authors.lastname: Nicholas
mesh_terms: D000375:Aging / Q000235:genetics*; D000818:Animals; D017173:Caenorhabditis elegans / Q000235:genetics* / Q000378:metabolism*; D005786:Gene Expression Regulation; D055786:Gene Knockout Techniques; D018869:Heat-Shock Response / Q000235:genetics; D007328:Insulin / Q000378:metabolism; D007334:Insulin-Like Growth Factor I / Q000378:metabolism; D007413:Intestinal Mucosa / Q000378:metabolism; D008136:Longevity / Q000235:genetics; D018384:Oxidative Stress / Q000235:genetics; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism*; D015398:Signal Transduction; D013312:Stress, Physiological / Q000235:genetics*
chemical_list: D007328:Insulin; D007334:Insulin-Like Growth Factor I; C102102:hematopoietic progenitor kinase 1; D017346:Protein Serine-Threonine Kinases