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 [1, 2]. Members of this protein family are serine/threonine kinases that are predominantly localised to the nucleus. Caenorhabditis elegans expresses a single HIPK protein, called HPK-1, which is broadly expressed and, like its mammalian counterparts, is localised to nuclear speckles, suggesting that it may be involved in analogous cellular processes. We have previously shown that HPK-1 is required for the promotion of germline proliferation during nematode development and into adulthood [3].Interestingly, HPK-1 was also reported as one of the proteins necessary for the extended lifespan of worm strains carrying a mutation in the gene encoding the insulin receptor
daf-2 [4]. To expand on this observation, phenotypic analyses are being conducted on a worm strain carrying a deletion mutation within
hpk-1, focusing on the tissue-specificity and molecular mechanisms by which HPK-1 may regulate various cellular processes, including ageing. The role of HPK-1 in stress responses is also being investigated, as observations of animals carrying a fosmid-based fluorescent reporter indicate that HPK-1 is induced under conditions of heat stress [3]. Additionally, a nuclear phosphoproteomic study by mass spectrometry is currently underway in order to identify potential HPK-1 phosphorylation targets. These putative targets will be tested for functional associations with HPK-1 in the context of ageing regulation and stress response.1. D'Orazi, G., et al., Homeodomain-interacting protein kinase-2 phosphorylates
p53 at Ser 46 and mediates apoptosis. Nat Cell Biol, 2002. 4(1): p. 11-19.2. Hofmann, T.G., et al., Regulation of
p53 activity by its interaction with homeodomain-interacting protein kinase-2. Nat Cell Biol, 2002. 4(1): p. 1-10.3. Berber, S., et al., Homeodomain interacting protein kinase (HPK-1) is required in the soma for robust germline proliferation in C. elegans. Dev Dyn, 2013.4. Samuelson, A.V., C.E. Carr, and G. Ruvkun, Gene activities that mediate increased life span of C. elegans insulin-like signaling mutants. Genes Dev, 2007. 21(22): p. 2976-94.