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000120012 0247_ $$2doi$$a10.1128/MCB.00766-14
000120012 0247_ $$2pmid$$apmid:25225333
000120012 0247_ $$2pmc$$apmc:PMC4248750
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000120012 0247_ $$2ISSN$$a1098-5549
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000120012 041__ $$aeng
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000120012 1001_ $$0P:(DE-HGF)0$$aFischer-Kešo, Regina$$b0$$eFirst author
000120012 245__ $$aPlakophilins 1 and 3 bind to FXR1 and thereby influence the mRNA stability of desmosomal proteins.
000120012 260__ $$aWashington, DC$$bSoc.$$c2014
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000120012 520__ $$aPlakophilins 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.
000120012 536__ $$0G:(DE-HGF)POF3-311$$a311 - Signalling pathways, cell and tumor biology (POF3-311)$$cPOF3-311$$fPOF III$$x0
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000120012 650_7 $$2NLM Chemicals$$aCarrier Proteins
000120012 650_7 $$2NLM Chemicals$$aDesmoplakins
000120012 650_7 $$2NLM Chemicals$$aFXR1 protein, human
000120012 650_7 $$2NLM Chemicals$$aG3BP protein, human
000120012 650_7 $$2NLM Chemicals$$aPABPC1L protein, human
000120012 650_7 $$2NLM Chemicals$$aPKP1 protein, human
000120012 650_7 $$2NLM Chemicals$$aPKP3 protein, human
000120012 650_7 $$2NLM Chemicals$$aPlakophilins
000120012 650_7 $$2NLM Chemicals$$aPoly(A)-Binding Proteins
000120012 650_7 $$2NLM Chemicals$$aRNA, Messenger
000120012 650_7 $$2NLM Chemicals$$aRNA-Binding Proteins
000120012 650_7 $$2NLM Chemicals$$aTrans-Activators
000120012 650_7 $$2NLM Chemicals$$aUPF1 protein, human
000120012 7001_ $$0P:(DE-HGF)0$$aBreuninger, Sonja$$b1
000120012 7001_ $$0P:(DE-HGF)0$$aHofmann, Sarah$$b2
000120012 7001_ $$0P:(DE-HGF)0$$aHenn, Manuela$$b3
000120012 7001_ $$aRöhrig, Theresa$$b4
000120012 7001_ $$aStröbel, Philipp$$b5
000120012 7001_ $$0P:(DE-HGF)0$$aStoecklin, Georg$$b6
000120012 7001_ $$0P:(DE-He78)0c4543046185361a644540fee0dad8b1$$aHofmann, Ilse$$b7$$eLast author$$udkfz
000120012 773__ $$0PERI:(DE-600)1474919-1$$a10.1128/MCB.00766-14$$gVol. 34, no. 23, p. 4244 - 4256$$n23$$p4244 - 4256$$tMolecular and cellular biology$$v34$$x1098-5549$$y2014
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