title: Plakophilins 1 and 3 bind to FXR1 and thereby influence the mRNA stability of desmosomal proteins.
abstract: Plakophilins 1 and 3 (PKP1/3) are members of the arm repeat family of catenin proteins and serve as structural components of desmosomes, which are important for cell-cell-adhesion. In addition, PKP1/3 occur as soluble proteins outside desmosomes, yet their role in the cytoplasm is not known. We found that cytoplasmic PKP1/3 coprecipitated with the RNA-binding proteins FXR1, G3BP, PABPC1, and UPF1, and these PKP1/3 complexes also comprised desmoplakin and PKP2 mRNAs. Moreover, we showed that the interaction of PKP1/3 with G3BP, PABPC1, and UPF1 but not with FXR1 was RNase sensitive. To address the cytoplasmic function of PKP1/3, we performed gain-and-loss-of-function studies. Both PKP1 and PKP3 knockdown cell lines showed reduced protein and mRNA levels for desmoplakin and PKP2. Whereas global rates of translation were unaffected, desmoplakin and PKP2 mRNA were destabilized. Furthermore, binding of PKP1/3 to FXR1 was RNA independent, and both PKP3 and FXR1 stabilized PKP2 mRNA. Our results demonstrate that cytoplasmic PKP1/3 are components of mRNA ribonucleoprotein particles and act as posttranscriptional regulators of gene expression.
authors.affiliation: Division of Vascular Oncology and Metastasis, German Cancer Research Center, DKFZ-ZMBH Alliance, Heidelberg, Germany Department of Vascular Biology and Tumor Angiogenesis, Medical Faculty Mannheim, Heidelberg University, Mannheim, Germany.
authors.forename: Regina
authors.initials: R
authors.lastname: Fischer-Kešo
authors.affiliation: Division of Vascular Oncology and Metastasis, German Cancer Research Center, DKFZ-ZMBH Alliance, Heidelberg, Germany Department of Vascular Biology and Tumor Angiogenesis, Medical Faculty Mannheim, Heidelberg University, Mannheim, Germany.
authors.forename: Sonja
authors.initials: S
authors.lastname: Breuninger
authors.affiliation: Helmholtz Junior Research Group, Posttranscriptional Control of Gene Expression, German Cancer Research Center, DKFZ-ZMBH Alliance, Heidelberg, Germany Center for Molecular Biology at the Heidelberg University, Heidelberg, Germany.
authors.forename: Sarah
authors.initials: S
authors.lastname: Hofmann
authors.affiliation: Department of Vascular Biology and Tumor Angiogenesis, Medical Faculty Mannheim, Heidelberg University, Mannheim, Germany.
authors.forename: Manuela
authors.initials: M
authors.lastname: Henn
authors.affiliation: Division of Vascular Oncology and Metastasis, German Cancer Research Center, DKFZ-ZMBH Alliance, Heidelberg, Germany.
authors.forename: Theresa
authors.initials: T
authors.lastname: Röhrig
authors.affiliation: Institute of Pathology, University Medical Center Göttingen, University Göttingen, Göttingen, Germany.
authors.forename: Philipp
authors.initials: P
authors.lastname: Ströbel
authors.affiliation: Helmholtz Junior Research Group, Posttranscriptional Control of Gene Expression, German Cancer Research Center, DKFZ-ZMBH Alliance, Heidelberg, Germany Center for Molecular Biology at the Heidelberg University, Heidelberg, Germany.
authors.forename: Georg
authors.initials: G
authors.lastname: Stoecklin
authors.affiliation: Division of Vascular Oncology and Metastasis, German Cancer Research Center, DKFZ-ZMBH Alliance, Heidelberg, Germany Department of Vascular Biology and Tumor Angiogenesis, Medical Faculty Mannheim, Heidelberg University, Mannheim, Germany i.hofmann@dkfz.de.
authors.forename: Ilse
authors.initials: I
authors.lastname: Hofmann
mesh_terms: D002352:Carrier Proteins / Q000378:metabolism; D002448:Cell Adhesion / Q000235:genetics; D002460:Cell Line; D004265:DNA Helicases; D051180:Desmoplakins / Q000235:genetics; D003896:Desmosomes / Q000235:genetics*; D055785:Gene Knockdown Techniques; D006801:Humans; D051191:Plakophilins / Q000235:genetics / Q000378:metabolism*; D039102:Poly(A)-Binding Proteins / Q000378:metabolism; D000075223:Poly-ADP-Ribose Binding Proteins; D011485:Protein Binding; D020365:RNA Helicases; D000067776:RNA Recognition Motif Proteins; D020871:RNA Stability / Q000235:genetics*; D012333:RNA, Messenger / Q000235:genetics; D016601:RNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D015534:Trans-Activators / Q000378:metabolism
chemical_list: D002352:Carrier Proteins; D051180:Desmoplakins; C096916:FXR1 protein, human; C531188:PABPC1L protein, human; C495335:PKP1 protein, human; C495339:PKP3 protein, human; D051191:Plakophilins; D039102:Poly(A)-Binding Proteins; D000075223:Poly-ADP-Ribose Binding Proteins; D000067776:RNA Recognition Motif Proteins; D012333:RNA, Messenger; D016601:RNA-Binding Proteins; D015534:Trans-Activators; D004265:DNA Helicases; C116070:G3BP1 protein, human; D020365:RNA Helicases; C101828:UPF1 protein, human