Hipk Is an Essential Protein That Promotes Notch Signal Transduction in the Drosophila Eye by Inhibition of the Global Co-Repressor Groucho

Dev Biol. 2009 Jan 1;325(1):263-72. doi: 10.1016/j.ydbio.2008.10.029. Epub 2008 Nov 5.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Apoptosis
  • Basic Helix-Loop-Helix Transcription Factors / antagonists & inhibitors*
  • Basic Helix-Loop-Helix Transcription Factors / chemistry
  • Basic Helix-Loop-Helix Transcription Factors / metabolism
  • Cell Proliferation
  • Clone Cells
  • DNA-Binding Proteins / genetics
  • DNA-Binding Proteins / metabolism
  • Drosophila Proteins / genetics
  • Drosophila Proteins / metabolism*
  • Drosophila melanogaster / cytology
  • Drosophila melanogaster / enzymology*
  • Drosophila melanogaster / growth & development
  • Eye / cytology
  • Eye / enzymology*
  • Eye / growth & development
  • Gene Expression Regulation, Developmental
  • Genes, Essential*
  • Molecular Sequence Data
  • Mutation / genetics
  • Phenotype
  • Phosphorylation
  • Protein Binding
  • Protein Kinases / genetics
  • Protein Kinases / metabolism*
  • Receptors, Notch / metabolism*
  • Repressor Proteins / antagonists & inhibitors*
  • Repressor Proteins / chemistry
  • Repressor Proteins / metabolism
  • Signal Transduction*


  • Basic Helix-Loop-Helix Transcription Factors
  • DNA-Binding Proteins
  • Drosophila Proteins
  • Receptors, Notch
  • Repressor Proteins
  • eyg protein, Drosophila
  • gro protein, Drosophila
  • Protein Kinases
  • HIPK protein, Drosophila