A β-Catenin Identified by Functional Rather Than Sequence Criteria and Its Role in Wnt/MAPK Signaling

Abstract

Wnt/MAPK signaling is a common variant of Wnt signaling in C. elegans and has been implicated in vertebrates. The sys-1 gene works with Wnt/MAPK signaling to control cell fates during C. elegans development. We report that the SYS-1 amino acid sequence is novel but that SYS-1 functions as beta-catenin: SYS-1 rescues a bar-1/beta-catenin null mutant, binds the POP-1/TCF beta-catenin binding domain, and coactivates POP-1-dependent transcription. Moreover, we provide genetic and molecular evidence that SYS-1 levels are crucial to POP-1 activity. Our results suggest that Wnt/MAPK signaling promotes POP-1 export from the nucleus to accommodate the limiting availability of its SYS-1/beta-catenin transcriptional coactivator. Discovery of SYS-1/beta-catenin extends our definition of beta-catenins and brings together aspects of the canonical mechanism for Wnt signaling with the noncanonical Wnt/MAPK mechanism. We discuss the idea that a similar pathway may be employed broadly in animal development.

FBF and Its Dual Control of gld-1 Expression in the Caenorhabditis elegans Germline

“…Plasmids encoding chimeric proteins were cotransformed into strain L40-ura3 (Invitrogen). Levels of 3-aminotriazole (3-AT) resistance were determined by assaying multiple independent transformants as described (Kidd et al 2005). Reporter (lacZ) expression was assayed using the Beta-Glo system (Promega).…”

The benefits of local depletion: The centrosome as a scaffold for ubiquitin-proteasome-mediated degradation

“…3 SYS-1/b-catenin is a transcription factor acting downstream of the Wnt signaling pathway to activate target genes necessary for cell fate specification. [75][76][77][78][79][80][81][82] During asymmetric division, SYS-1 is targeted to mitotic centrosomes by its interaction with the centrosomal protein RSA-2. 83 Disrupting SYS-1 centrosomal localization by depletion of RSA-2 leads to increased SYS-1 retention by daughter cells after division, indicating the presence of a negative regulatory mechanism involving centrosomal targeting.…”

Wnt signaling through T-cell factor phosphorylation

“…This POP-1 asymmetry requires LIT-1, a protein kinase that regulates asymmetric cell divisions [50] and promotes the nuclear export of POP-1 [49,51,52]. Paradoxically, the small amount of POP-1 that remains in the E-cell nucleus is required, together with SYS-1, a distant member of the β-catenin family [53,54], for Wnt-dependent activation of endoderm-specific end-1 and end-3 target genes [44,45,47,[55][56][57]. POP-1 also functions as a transcriptional activator in T neuroblasts and somatic gonadal precursors, in which POP-1 and SYS-1 directly activate the ceh-22/tinman gene [47,53,54,58].…”