RRC ID 33068
Author Reim G, Hruzova M, Goetze S, Basler K.
Title Protection of armadillo/β-Catenin by armless, a novel positive regulator of wingless signaling.
Journal PLoS Biol.
Abstract The Wingless (Wg/Wnt) signaling pathway is essential for metazoan development, where it is central to tissue growth and cellular differentiation. Deregulated Wg pathway activation underlies severe developmental abnormalities, as well as carcinogenesis. Armadillo/β-Catenin plays a key role in the Wg transduction cascade; its cytoplasmic and nuclear levels directly determine the output activity of Wg signaling and are thus tightly controlled. In all current models, once Arm is targeted for degradation by the Arm/β-Catenin destruction complex, its fate is viewed as set. We identified a novel Wg/Wnt pathway component, Armless (Als), which is required for Wg target gene expression in a cell-autonomous manner. We found by genetic and biochemical analyses that Als functions downstream of the destruction complex, at the level of the SCF/Slimb/βTRCP E3 Ub ligase. In the absence of Als, Arm levels are severely reduced. We show by biochemical and in vivo studies that Als interacts directly with Ter94, an AAA ATPase known to associate with E3 ligases and to drive protein turnover. We suggest that Als antagonizes Ter94's positive effect on E3 ligase function and propose that Als promotes Wg signaling by rescuing Arm from proteolytic degradation, spotlighting an unexpected step where the Wg pathway signal is modulated.
Volume 12(11)
Pages e1001988
Published 2014-11
DOI 10.1371/journal.pbio.1001988
PMID 25369031
PMC PMC4219662
MeSH Animals Armadillo Domain Proteins / metabolism* Carrier Proteins / metabolism Cell Cycle Proteins / metabolism Drosophila Drosophila Proteins / metabolism* Gene Expression Regulation, Developmental HEK293 Cells Hedgehog Proteins / metabolism Humans Intracellular Signaling Peptides and Proteins / metabolism* Receptors, Notch / metabolism Transcription Factors / metabolism* Ubiquitin-Protein Ligases / metabolism Valosin Containing Protein Wings, Animal / growth & development Wnt Proteins / metabolism* Wnt1 Protein / metabolism* beta Catenin / metabolism*
IF 8.386
Times Cited 1
Drosophila 3060R-3