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

MD Meneghini, T Ishitani, JC Carter, N Hisamoto… - Nature, 1999 - nature.com
MD Meneghini, T Ishitani, JC Carter, N Hisamoto, J Ninomiya-Tsuji, CJ Thorpe, DR Hamill…
Nature, 1999nature.com
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 (,,). Here we
show that the genes mom-4 and lit-1 are also required to downregulate POP-1, not only in E …
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 (, , ). 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 .
nature.com