Journal Article DKFZ-2017-00600

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Plakophilins 1 and 3 bind to FXR1 and thereby influence the mRNA stability of desmosomal proteins.

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2014
Soc. Washington, DC

Molecular and cellular biology 34(23), 4244 - 4256 () [10.1128/MCB.00766-14]
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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.

Keyword(s): Carrier Proteins ; Desmoplakins ; FXR1 protein, human ; G3BP protein, human ; PABPC1L protein, human ; PKP1 protein, human ; PKP3 protein, human ; Plakophilins ; Poly(A)-Binding Proteins ; RNA, Messenger ; RNA-Binding Proteins ; Trans-Activators ; UPF1 protein, human

Classification:

Contributing Institute(s):
  1. Vaskuläre Onkologie und Metastasierung (A190)
  2. Posttranskriptionelle Genregulation (A200)
Research Program(s):
  1. 311 - Signalling pathways, cell and tumor biology (POF3-311) (POF3-311)

Appears in the scientific report 2014
Database coverage:
Medline ; BIOSIS Previews ; Current Contents - Life Sciences ; Ebsco Academic Search ; IF < 5 ; JCR ; NCBI Molecular Biology Database ; SCOPUS ; Science Citation Index ; Science Citation Index Expanded ; Thomson Reuters Master Journal List ; Web of Science Core Collection
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 Record created 2017-03-28, last modified 2024-02-28


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