Regulation of the Hedgehog and Wingless signalling pathways by the F- box/WD40-repeat protein Slimb

Jin Jiang, Gary Struhl

Research output: Contribution to journalArticlepeer-review

516 Scopus citations

Abstract

Members of the Hedgehog (Hh) and Wnt/Wingless (Wg) families of secreted proteins control many aspects of growth and patterning during animal development. Hh signal transduction leads to increased stability of a transcription factor, Cubitus interruptus (Gi), whereas Wg signal transduction causes increased stability of Armadillo (Arm/β-catenin), a possible co-factor for the transcriptional regulator Lef1/TGF. Here we describe a new gene, slimb (for supernumerary limbs), which negatively regulates both of these signal transduction pathways. Loss of function of slimb results in a cell-autonomous accumulation of high levels of both Ci and Arm, and the ectopic expression of both Hh- and Wg- responsive genes. The slimb gene encodes a conserved F-box/WD40-repeat protein related to Cdc4p, a protein in budding yeast that targets cell-cycle regulators for degradation by the ubiquitin/proteasome pathway. We propose that Slimb protein normally targets Ci and Arm for processing or degradation by the ubiquitin/proteasome pathway, and that Hh and Wg regulate gene expression at least in part by inducing changes in Ci and Arm, which protect them from Slimb-mediated proteolysis.

Original languageEnglish (US)
Pages (from-to)493-496
Number of pages4
JournalNature
Volume391
Issue number6666
DOIs
StatePublished - Jan 29 1998

ASJC Scopus subject areas

  • General

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