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

Marc D. Meneghini, Tohru Ishitani, J. Clayton Carter, Naoki Hisamoto, Jun Ninomiya-Tsuji, Christopher J. Thorpe, Danlelle R. Hamill, Kunihiro Matsumoto, Bruce Bowerman

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229 Citations (Scopus)

Abstract

The signalling protein Wnt regulates transcription factors containing high-mobility-group (HMG) domains to direct decisions on cell fate during animal development. In Caenorhabditis elegans, the HMG-domain-containing repressor POP-1 distinguishes the fates of anterior daughter cells from their posterior sisters throughout development, and Wnt signalling downregulates POP-1 activity in one posterior daughter cell called E (refs 2, 4, 5). Here we show that the genes more-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).

Original languageEnglish
Pages (from-to)793-797
Number of pages5
JournalNature
Volume399
Issue number6738
DOIs
Publication statusPublished - Jun 24 1999

All Science Journal Classification (ASJC) codes

  • General

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    Meneghini, M. D., Ishitani, T., Carter, J. C., Hisamoto, N., Ninomiya-Tsuji, J., Thorpe, C. J., Hamill, D. R., Matsumoto, K., & Bowerman, B. (1999). Map kinase and Wnt pathways converge to downregulate an HMG-domain repressor in Caenorhabditis elegans. Nature, 399(6738), 793-797. https://doi.org/10.1038/21666