Abstract
The signalling protein Wnt regulates transcription factors containing high-mobility-group (HMG) domains to direct decisions on cell fate during animal development1. In Caenorhabditis elegans, the HMG-domain-containing repressor POP-1 distinguishes the fates of anterior daughter cells from their posterior sisters throughout development2,3, and Wnt signalling downregulates POP-1 activity in one posterior daughter cell called E (refs 2, 4, 5). Here we show that the genes mom-4 and lit-1 are also required to downregulate POP-1, not only in E but also in other posterior daughter cells. Consistent with action in a common pathway, mom-4 and lit-1 exhibit similar mutant phenotypes and encode components of the mitogen-activated protein kinase (MAPK) pathway that are homologous to vertebrate transforming-growth-factor-β-activated kinase (TAK1) and NEMO-like kinase (NLK), respectively. Furthermore, MOM-4 and TAK1 bind related proteins that promote their kinase activities. 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-containing proteins related to POP-1 (ref. 6).
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Acknowledgements
We thank J. Willis for assistance with POP-1 antibody staining; D. Miller, R. Lin and J. Ahringer for providing antibodies; the C. elegans Genetics center, funded by the NIH National Center for Research Resources, for providing strains; H. and R. Schnabel for the t1534 lit-1 allele; and B. Draper and C. Doe for helpful comments on the manuscript. B.B. is supported by an NIH R01 grant and M.M. by an NIH Genetics training grant.
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Meneghini, M., Ishitani, T., Carter, J. et al. MAP kinase and Wnt pathways converge to downregulate an HMG-domain repressor in Caenorhabditis elegans. Nature 399, 793–797 (1999). https://doi.org/10.1038/21666
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DOI: https://doi.org/10.1038/21666
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