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

Regulation of the Hedgehog and Wingless signalling pathways by the F-box/WD40-repeat protein Slimb Members of the Hedgehog (Hh) and Wnt/Wingless (Wg) families of secreted proteins control many aspects of growth and patterning during animal development 1 , 2 . Hh signal transduction leads to increased stability of a transcription factor, Cubitus interruptus (Ci) 3 , 4 , whereas Wg signal transduction causes increased stability of Armadillo (Arm/β-catenin) 5 , a possible co-factor for thetranscriptional regulator Lef1/TCF 6 . 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 7,8,9 . We propose that Slimb protein normally targets Ci and Arm for processing or degradation by the ubiquitin/proteasomepathway, 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. http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png Nature Springer Journals

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

Jiang, Jin; Struhl, Gary
Nature , Volume 391 (6666) – Jan 29, 1998
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References (34)

Publisher
Springer Journals
Copyright
Copyright © 1998 by Macmillan Magazines Ltd.
Subject
Science, Humanities and Social Sciences, multidisciplinary; Science, Humanities and Social Sciences, multidisciplinary; Science, multidisciplinary
ISSN
0028-0836
eISSN
1476-4687
DOI
10.1038/35154
Publisher site
See Article on Publisher Site

Abstract

Members of the Hedgehog (Hh) and Wnt/Wingless (Wg) families of secreted proteins control many aspects of growth and patterning during animal development 1 , 2 . Hh signal transduction leads to increased stability of a transcription factor, Cubitus interruptus (Ci) 3 , 4 , whereas Wg signal transduction causes increased stability of Armadillo (Arm/β-catenin) 5 , a possible co-factor for thetranscriptional regulator Lef1/TCF 6 . 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 7,8,9 . We propose that Slimb protein normally targets Ci and Arm for processing or degradation by the ubiquitin/proteasomepathway, 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.

Journal

Nature – Springer Journals

Published: Jan 29, 1998

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