title: Hipk is an essential protein that promotes Notch signal transduction in the Drosophila eye by inhibition of the global co-repressor Groucho.
abstract: Homeodomain interacting protein kinase (Hipk) is a member of a novel family of serine/threonine kinases. Extensive biochemical studies of vertebrate homologs, particularly Hipk2, have identified a growing list of interactors, including proteins involved in transcriptional regulation, chromatin remodeling and essential signaling pathways such as Wnt and TGFbeta. To gain insight into the in vivo functions of the single Drosophila Hipk we characterized loss of function alleles, which revealed an essential requirement for hipk. We find that in the developing eye, hipk promotes the Notch pathway. Notch signaling acts at multiple points in eye development to promote growth, proliferation and patterning. Hipk stimulates the early function of Notch in promotion of global growth of the eye disc. It has been shown in the Drosophila eye that Hipk interferes with the repressive activity of the global co-repressor, Groucho (Gro). Here, we propose that Hipk antagonizes Gro to promote the transmission of the Notch signal, indicating that Hipk plays numerous roles in regulating gene expression through interference with the formation of Gro-containing co-repressor complexes.
authors.affiliation: Department of Molecular Biology and Biochemistry, Simon Fraser University, Burnaby, British Columbia, Canada.
authors.forename: Wendy
authors.initials: W
authors.lastname: Lee
authors.forename: Bryan C
authors.initials: BC
authors.lastname: Andrews
authors.forename: Michael
authors.initials: M
authors.lastname: Faust
authors.forename: Uwe
authors.initials: U
authors.lastname: Walldorf
authors.forename: Esther M
authors.initials: EM
authors.lastname: Verheyen
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D017209:Apoptosis; D051792:Basic Helix-Loop-Helix Proteins / Q000037:antagonists & inhibitors* / Q000737:chemistry / Q000378:metabolism; D049109:Cell Proliferation; D002999:Clone Cells; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism; D029721:Drosophila Proteins / Q000235:genetics / Q000378:metabolism*; D004331:Drosophila melanogaster / Q000166:cytology / Q000201:enzymology* / Q000254:growth & development; D005123:Eye / Q000166:cytology / Q000201:enzymology* / Q000254:growth & development; D018507:Gene Expression Regulation, Developmental; D020043:Genes, Essential; D008969:Molecular Sequence Data; D009154:Mutation / Q000235:genetics; D010641:Phenotype; D010766:Phosphorylation; D011485:Protein Binding; D011494:Protein Kinases / Q000235:genetics / Q000378:metabolism*; D051880:Receptors, Notch / Q000378:metabolism*; D012097:Repressor Proteins / Q000037:antagonists & inhibitors* / Q000737:chemistry / Q000378:metabolism; D015398:Signal Transduction
chemical_list: D051792:Basic Helix-Loop-Helix Proteins; D004268:DNA-Binding Proteins; D029721:Drosophila Proteins; D011494:Protein Kinases; D051880:Receptors, Notch; D012097:Repressor Proteins; C477040:eyg protein, Drosophila; C091023:gro protein, Drosophila; C501861:HIPK protein, Drosophila