Frodo links Dishevelled to the p120-catenin/Kaiso pathway: distinct catenin subfamilies promote Wnt signals.
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/beta-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 beta-catenin, and that each catenin promotes its respective signal in parallel to regulate distinct, as well as shared, direct downstream gene targets.
Park
Jae-il
JI
Department of Biochemistry and Molecular Biology and Program in Genes and Development, University of Texas M.D. Anderson Cancer Center, Houston, Texas 77030, USA.
Ji
Hong
H
Jun
Sohee
S
Gu
Dongmin
D
Hikasa
Hiroki
H
Li
Lei
L
Sokol
Sergei Y
SY
McCrea
Pierre D
PD
D048868:Adaptor Proteins, Signal Transducing / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D002352:Carrier Proteins / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D051177:Catenins; D015815:Cell Adhesion Molecules / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D002467:Cell Nucleus / Q000378:metabolism; D000072261:Dishevelled Proteins; D004625:Embryo, Nonmammalian; D066298:In Vitro Techniques; D010750:Phosphoproteins / Q000235:genetics / Q000378:metabolism* / Q000502:physiology*; D011485:Protein Binding; D021381:Protein Transport; D012097:Repressor Proteins / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D015398:Signal Transduction; D020798:Two-Hybrid System Techniques; D051153:Wnt Proteins / Q000235:genetics / Q000502:physiology*; D029867:Xenopus Proteins / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D014982:Xenopus laevis; D000095002:Delta Catenin
D048868:Adaptor Proteins, Signal Transducing; D002352:Carrier Proteins; D051177:Catenins; D015815:Cell Adhesion Molecules; C454443:DACT1 protein, Xenopus; C000606586:DVL1 protein, Xenopus; D000072261:Dishevelled Proteins; D010750:Phosphoproteins; D012097:Repressor Proteins; D051153:Wnt Proteins; D029867:Xenopus Proteins; C451401:ZBTB33 protein, Xenopus; D000095002:Delta Catenin