TY - JOUR
T1 - Frodo Links Dishevelled to the p120-Catenin/Kaiso Pathway
T2 - Distinct Catenin Subfamilies Promote Wnt Signals
AU - Park, Jae il
AU - Ji, Hong
AU - Jun, Sohee
AU - Gu, Dongmin
AU - Hikasa, Hiroki
AU - Li, Lei
AU - Sokol, Sergei Y.
AU - McCrea, Pierre D D.
N1 - Funding Information:
We thank Barbara K. Brott for the yeast two-hybrid assay; Weilin Wu for assistance with preparing anti-Frodo antibodies; Juliet M. Daniel, Michelle C. Barton, Warren S.-L. Liao, Andreas Bergmann, and Mong-Hong Lee for constructive comments; Albert B. Reynolds (Vanderbilt University) for providing anti-p120-catenin antibody; and Jon P. Lyons, Kyucheol Cho, and Mariam Khalil for helpful reading of the manuscript. This work was supported by National Institutes of Health RO1 (GM52112), a Texas ARP Grant, and an Institutional Research Grant. DNA sequencing and other core facilities were supported by a University of Texas M.D. Anderson Cancer Center National Cancer Institute Core Grant CA-16672. J.P. is a Rosalie B. Hite graduate fellow.
PY - 2006/11
Y1 - 2006/11
N2 - p120-catenin is an Arm repeat protein that interacts with varied components such as cadherin, small G proteins, kinases, and the Kaiso transcriptional repressor. Despite recent advances in understanding the roles that p120-catenin and Kaiso play in downstream modulation of Wnt/β-catenin signaling, the identity of the upstream regulators of the p120-catenin/Kaiso pathway have remained unclear. Here, we find that p120-catenin binds Frodo, which itself interacts with the Wnt pathway protein Dishevelled (Dsh). In Xenopus laevis, we demonstrate that Wnt signals result in Frodo-mediated stabilization of p120-catenin, which, in turn, promotes Kaiso sequestration or removal from the nucleus. Our results point to Dsh and Frodo as upstream regulators of the p120-catenin/Kaiso signaling pathway. Importantly, this suggests that Wnt signals acting through Dsh regulate the stability of p120-catenin in addition to that of β-catenin, and that each catenin promotes its respective signal in parallel to regulate distinct, as well as shared, direct downstream gene targets.
AB - p120-catenin is an Arm repeat protein that interacts with varied components such as cadherin, small G proteins, kinases, and the Kaiso transcriptional repressor. Despite recent advances in understanding the roles that p120-catenin and Kaiso play in downstream modulation of Wnt/β-catenin signaling, the identity of the upstream regulators of the p120-catenin/Kaiso pathway have remained unclear. Here, we find that p120-catenin binds Frodo, which itself interacts with the Wnt pathway protein Dishevelled (Dsh). In Xenopus laevis, we demonstrate that Wnt signals result in Frodo-mediated stabilization of p120-catenin, which, in turn, promotes Kaiso sequestration or removal from the nucleus. Our results point to Dsh and Frodo as upstream regulators of the p120-catenin/Kaiso signaling pathway. Importantly, this suggests that Wnt signals acting through Dsh regulate the stability of p120-catenin in addition to that of β-catenin, and that each catenin promotes its respective signal in parallel to regulate distinct, as well as shared, direct downstream gene targets.
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U2 - 10.1016/j.devcel.2006.09.022
DO - 10.1016/j.devcel.2006.09.022
M3 - Article
C2 - 17084360
AN - SCOPUS:33750469721
SN - 1534-5807
VL - 11
SP - 683
EP - 695
JO - Developmental cell
JF - Developmental cell
IS - 5
ER -