TY - JOUR
T1 - Phosphorylation by the β-catenin/MAPK complex promotes 14-3-3-mediated nuclear export of TCF/POP-1 in signal-responsive cells in C. elegans
AU - Lo, Miao Chia
AU - Gay, Frédérique
AU - Odom, Raanan
AU - Shi, Yang
AU - Lin, Rueyling
N1 - Funding Information:
The authors would like to thank Drs. Scott Robertson, Keith Wharton, and Eric Olson for their comments on the manuscript; Melanie Reuben and Dominica Calvo for technical assistance; and Morris Maduro, Joel Rothman, Andy Golden, Diane Shakes, Geraldine Seydoux, Ken Kemphues, Craig Mello, and Andy Fire for various reagents. M-C.L., R.O., and R.L. are supported by the NIH grant (HD37933) (to R.L.). R.L. is also supported by a grant from March of Dimes (FY01-265). F.G. and Y.S. are supported by the grant GM58012 to Y.S.
PY - 2004/4/2
Y1 - 2004/4/2
N2 - In C. elegans embryos, a Wnt/MAPK signaling pathway downregulates the TCF/LEF transcription factor POP-1, resulting in a lower nuclear level in signal-responsive cells compared to their sisters. Although the β-catenin WRM-1 is required for POP-1 downregulation, a direct interaction between these two proteins does not seem to be required, as the β-catenin-interacting domain of POP-1 is dispensable for both POP-1 downregulation and function in early embryos. We show here that WRM-1 downregulates POP-1 by promoting its phosphorylation by the MAP kinase LIT-1 and subsequent nuclear export via a 14-3-3 protein, PAR-5. In signal-responsive cells, we also detect a concurrent upregulation of nuclear LIT-1 that is dependent on Wnt/MAPK signaling. Our results suggest a model whereby Wnt/MAPK signaling downregulates POP-1 levels in responsive cells, in part by increasing nuclear LIT-1 levels, thereby increasing POP-1 phosphorylation and PAR-5-mediated nuclear export.
AB - In C. elegans embryos, a Wnt/MAPK signaling pathway downregulates the TCF/LEF transcription factor POP-1, resulting in a lower nuclear level in signal-responsive cells compared to their sisters. Although the β-catenin WRM-1 is required for POP-1 downregulation, a direct interaction between these two proteins does not seem to be required, as the β-catenin-interacting domain of POP-1 is dispensable for both POP-1 downregulation and function in early embryos. We show here that WRM-1 downregulates POP-1 by promoting its phosphorylation by the MAP kinase LIT-1 and subsequent nuclear export via a 14-3-3 protein, PAR-5. In signal-responsive cells, we also detect a concurrent upregulation of nuclear LIT-1 that is dependent on Wnt/MAPK signaling. Our results suggest a model whereby Wnt/MAPK signaling downregulates POP-1 levels in responsive cells, in part by increasing nuclear LIT-1 levels, thereby increasing POP-1 phosphorylation and PAR-5-mediated nuclear export.
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U2 - 10.1016/S0092-8674(04)00203-X
DO - 10.1016/S0092-8674(04)00203-X
M3 - Article
C2 - 15066285
AN - SCOPUS:1842715734
SN - 0092-8674
VL - 117
SP - 95
EP - 106
JO - Cell
JF - Cell
IS - 1
ER -