HOMEODOMAIN INTERACTING PROTEIN KINASE 2, HIPK2, REGULATES THE EXPRESSION OF GABAergic NEURONS IN THE CEREBELLUM AND CONTROLS SHORT AND WORKING MEMORY

Homeodomain-interacting protein kinase (HIPK1-4) is a family of nuclear serine/threonine kinase, that regulating by gene transcription, affects cell proliferation, differentiation, and apoptosis. HIPK1-3 were originally described as co-repressors for homeobox transcription factors, in addition, they can interact with and/or phosphorylate several transcriptional regulators. HIPK2 is activated in response to DNA damage, including UV radiation and chemotherapeutic drugs and phosphorylates p53 to promote the transcription of pro-apoptotic p53 target genes. In addition, HIPK2 interacts with a number of transcription factors that control developmental processes, tumor suppression and apoptosis. The kinase is regulated by both sumoylation and ubiquitination. Ubiquitination and subsequent degradation of HIPK2 is inhibited by DNA damaging agents. Caspase-dependent cleavage of HIPK2 removes the inhibitory domain and results in enhanced HIPK2 activity. In the present study we have firstly characterized the expression profile of HIPK2 in different brain regions of adult wild type (wt) and HIPK2 Knockout (KO mice). Then, we have carried out behavioral experiments in order to establish the role of HIPK2 in several brain functions.