Hipk proteins dually regulate Wnt/Wingless signal transduction.
The Wnt/Wingless (Wg) pathway is an evolutionarily conserved signaling system that is used reiteratively, both spatially and temporally, to control the development of multicellular animals. The stability of cytoplasmic β-catenin/Armadillo, the transcriptional effector of the pathway, is controlled by sequential N-terminal phosphorylation and ubiquitination that targets it for proteasome-mediated degradation. Orthologous members of the Homeodomain-interacting protein kinase family from Drosophila to vertebrates have been implicated in the regulation of Wnt/Wingless signaling. In Drosophila, as a consequence of Hipk activity, cells accumulate stabilized Armadillo that directs the expression of Wg-specific target genes. Hipk promotes the stabilization of Armadillo by inhibiting its ubiquitination (and hence subsequent degradation) by the SCF(Slimb) E3 ubiquitin ligase complex. Vertebrate Hipk2 impedes β-catenin ubiquitination to promote its stability and the Wnt signal in a mechanism that is functionally conserved. Moreover, we describe here that Hipk proteins have a role independent of their effect on β-catenin/Armadillo stability to enhance Wnt/Wingless signaling.
Department of Molecular Biology and Biochemistry, Simon Fraser University, Burnaby, BC, Canada.
Esther M
EM
Verheyen
Sharan
S
Swarup
Wendy
W
Lee
D000818:Animals; D051186:Armadillo Domain Proteins / Q000378:metabolism; D018797:Cell Cycle Proteins / Q000378:metabolism; D004330:Drosophila / Q000254:growth & development / Q000378:metabolism*; D029721:Drosophila Proteins / Q000378:metabolism*; D053823:Hedgehog Proteins / Q000378:metabolism; D011494:Protein Kinases / Q000378:metabolism*; D015398:Signal Transduction; D014157:Transcription Factors / Q000378:metabolism; D044767:Ubiquitin-Protein Ligases / Q000378:metabolism; D051153:Wnt Proteins / Q000378:metabolism*; D051155:Wnt1 Protein / Q000378:metabolism*; D044844:beta-Transducin Repeat-Containing Proteins / Q000378:metabolism
C495305:ARM protein, Drosophila; D051186:Armadillo Domain Proteins; D018797:Cell Cycle Proteins; D029721:Drosophila Proteins; D053823:Hedgehog Proteins; D014157:Transcription Factors; D051153:Wnt Proteins; D051155:Wnt1 Protein; D044844:beta-Transducin Repeat-Containing Proteins; C110233:slmb protein, Drosophila; C074622:wg protein, Drosophila; C077245:hh protein, Drosophila; D044767:Ubiquitin-Protein Ligases; D011494:Protein Kinases; C501861:HIPK protein, Drosophila