Plakophilin-3 catenin associates with the ETV1/ER81 transcription factor to positively modulate gene activity.
Members of the plakophilin-catenin sub-family (Pkp-1, -2, and -3) facilitate the linkage of desmosome junctional components to each other (e.g. desmosomal cadherins to desmoplakin) and the intermediate-filament cytoskeleton. Pkps also contribute to desmosomal stabilization and the trafficking of its components. The functions of Pkps outside of the desmosome are less well studied, despite evidence suggesting their roles in mRNA regulation, small-GTPase modulation (e.g. mid-body scission) during cell division, and cell survival following DNA damage. Pkp-catenins are further believed to have roles in the nucleus given their nuclear localization in some contexts and the known nuclear roles of structurally related catenins, such as beta-catenin and p120-catenin. Further, Pkp-catenin activities in the nuclear compartment have become of increased interest with the identification of interactions between Pkp2-catenin and RNA Pol III and Pkp1 with single-stranded DNA. Consistent with earlier reports suggesting possible nuclear roles in development, we previously demonstrated prominent nuclear localization of Pkp3 in Xenopus naïve ectoderm ("animal cap") cells and recently resolved a similar localization in mouse embryonic stem cells. Here, we report the association and positive functional interaction of Pkp3 with a transcription factor, Ets variant gene 1 (ETV1), which has critical roles in neural development and prominent roles in human genetic disease. Our results are the first to report the interaction of a sequence-specific transcription factor with any Pkp. Using Xenopus laevis embryos and mammalian cells, we provide evidence for the Pkp3:ETV1 complex on both biochemical and functional levels.
Department of Biochemistry and Molecular Biology, The University of Texas M.D. Anderson Cancer Center, Houston, Texas, United States of America ; Program in Genes & Development, The University of Texas Graduate School of Biomedical Science - Houston, Texas, United States of America.
William A
WA
Munoz
Department of Biochemistry and Molecular Biology, The University of Texas M.D. Anderson Cancer Center, Houston, Texas, United States of America ; Program in Genes & Development, The University of Texas Graduate School of Biomedical Science - Houston, Texas, United States of America.
Moonsup
M
Lee
Department of Biochemistry and Molecular Biology, The University of Texas M.D. Anderson Cancer Center, Houston, Texas, United States of America.
Rachel K
RK
Miller
Department of Biochemistry and Molecular Biology, The University of Texas M.D. Anderson Cancer Center, Houston, Texas, United States of America ; Center for Biomolecular Structure and Function, The University of Texas M.D. Anderson Cancer Center, Houston, Texas, United States of America.
Zamal
Z
Ahmed
Department of Biochemistry and Molecular Biology, The University of Texas M.D. Anderson Cancer Center, Houston, Texas, United States of America.
Hong
H
Ji
Department of Biochemistry and Molecular Biology, The University of Texas M.D. Anderson Cancer Center, Houston, Texas, United States of America ; Center for Biomolecular Structure and Function, The University of Texas M.D. Anderson Cancer Center, Houston, Texas, United States of America.
Todd M
TM
Link
Department of Biochemistry and Molecular Biology, The University of Texas M.D. Anderson Cancer Center, Houston, Texas, United States of America ; Center for Biomolecular Structure and Function, The University of Texas M.D. Anderson Cancer Center, Houston, Texas, United States of America.
Gilbert R
GR
Lee
Department of Biochemistry and Molecular Biology, The University of Texas M.D. Anderson Cancer Center, Houston, Texas, United States of America ; Department of Surgery, Houston Methodist, Houston Methodist Research Institute, Houston, Texas, United States of America.
Malgorzata
M
Kloc
Department of Biochemistry and Molecular Biology, The University of Texas M.D. Anderson Cancer Center, Houston, Texas, United States of America ; Program in Genes & Development, The University of Texas Graduate School of Biomedical Science - Houston, Texas, United States of America ; Center for Biomolecular Structure and Function, The University of Texas M.D. Anderson Cancer Center, Houston, Texas, United States of America.
John E
JE
Ladbury
Department of Biochemistry and Molecular Biology, The University of Texas M.D. Anderson Cancer Center, Houston, Texas, United States of America ; Program in Genes & Development, The University of Texas Graduate School of Biomedical Science - Houston, Texas, United States of America.
Pierre D
PD
McCrea
D000818:Animals; D002467:Cell Nucleus / Q000378:metabolism*; D017931:DNA Primers / Q000235:genetics; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D004625:Embryo, Nonmammalian / Q000378:metabolism; D005455:Fluorescent Antibody Technique; D005786:Gene Expression Regulation / Q000235:genetics*; D057809:HEK293 Cells; D006367:HeLa Cells; D006801:Humans; D015151:Immunoblotting; D047468:Immunoprecipitation; D017403:In Situ Hybridization; D051379:Mice; D051191:Plakophilins / Q000378:metabolism*; D060888:Real-Time Polymerase Chain Reaction; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*; D020798:Two-Hybrid System Techniques; D014982:Xenopus laevis
D017931:DNA Primers; D004268:DNA-Binding Proteins; C095239:ETV1 protein, human; D051191:Plakophilins; D014157:Transcription Factors