Evidence for the direct involvement of {beta}TrCP in Gli3 protein processing. Academic Article Article uri icon

Overview

MeSH

  • Casein Kinase I
  • Cells, Cultured
  • Glycogen Synthase Kinase 3
  • Humans
  • Phosphorylation

MeSH Major

  • Kruppel-Like Transcription Factors
  • Nerve Tissue Proteins
  • Protein Processing, Post-Translational
  • beta-Transducin Repeat-Containing Proteins

abstract

  • Hedgehog-regulated processing of the transcription factor cubitus interruptus (Ci) in Drosophila depends on phosphorylation of the C-terminal region of Ci by cAMP-dependent protein kinase and subsequently by casein kinase 1 and glycogen synthase kinase 3. Ci processing also requires Slimb, an F-box protein of SCF (Skp1/Cullin/F-box proteins) complex, and the proteasome, but the interplay between phosphorylation and the activity of Slimb and the proteasome remains unclear. Here we show that processing of the Gli3 protein, a homolog of Ci, also depends on phosphorylation of a set of four cAMP-dependent protein kinase sites that primes subsequent phosphorylation of adjacent casein kinase 1 and glycogen synthase kinase 3. Our gain- and loss-of-function analyses in cultured cells further reveal that betaTrCP, the vertebrate homolog of Slimb, is required for Gli3 processing, and we demonstrate that betaTrCP can bind phosphorylated Gli3 both in vitro and in vivo. We also find that the Gli3 protein is polyubiquitinated in the cell and that its processing depends on proteasome activity. Our findings provide evidence for a direct link between phosphorylation of Gli3/Ci proteins and betaTrCP/Slimb action, thus supporting the hypothesis that the processing of Gli3/Ci is affected by the proteasome.

publication date

  • January 3, 2006

has subject area

  • Casein Kinase I
  • Cells, Cultured
  • Glycogen Synthase Kinase 3
  • Humans
  • Kruppel-Like Transcription Factors
  • Nerve Tissue Proteins
  • Phosphorylation
  • Protein Processing, Post-Translational
  • beta-Transducin Repeat-Containing Proteins

Research

keywords

  • Comparative Study
  • Journal Article

Identity

Language

  • eng

PubMed Central ID

  • PMC1325010

Digital Object Identifier (DOI)

  • 10.1073/pnas.0509927103

PubMed ID

  • 16371461

Additional Document Info

start page

  • 33

end page

  • 38

volume

  • 103

number

  • 1