MAP kinase and Wnt pathways converge to downregulate an HMG-domain repressor in Caenorhabditis elegans

The signalling protein Wnt regulates transcription factors containing high- mobility-group (HMG) domains to direct decisions on cell fate during animal development(1). In Caenorhabditis elegans, the HMG-domain-containing repre ssor POP-1 distinguishes the fates of anterior daughter cells from their po sterior sisters throughout development(2,3), and Wnt signalling downregulat es POP-1 activity in one posterior daughter cell called E (refs 2, 4, 5). H ere we show that the genes mom-4 and lit-1 are also required to downregulat e POP-1, not only in E but also in other posterior daughter cells. Consiste nt with action in a common pathway, mom-4 and lit-1 exhibit similar mutant phenotypes and encode components of the mitogen-activated protein kinase (M APK) pathway that are homologous to vertebrate transforming-growth-factor-b eta-activated kinase (TAK1) and NEMO-like kinase (NLK), respectively. Furth ermore, MOM-4 and TAK1 bind related proteins that promote their kinase acti vities. We conclude that: a MAPK-related pathway cooperates with Wnt signal transduction to downregulate POP-1 activity. These functions are likely to be conserved in vertebrates, as TAK1 and NLK can downregulate HMG-domain-c ontaining proteins related to POP-1 (ref. 6).