Plakophilin 1 stimulates translation by promoting eIF4A1 activity |
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Authors: | Annika Wolf Malgorzata Krause-Gruszczynska Olaf Birkenmeier Antje Ostareck-Lederer Stefan Hüttelmaier Mechthild Hatzfeld |
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Affiliation: | 1.Division of Pathobiochemistry, 2.Institute for Biotechnology, and 3.Department of Molecular Cell Biology, Martin Luther University Halle-Wittenberg, 06097 Halle, Germany;4.University Hospital Aachen, 52074 Aachen, Germany |
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Abstract: | Plakophilins 1–3 (PKP1–3) are desmosomal proteins of the p120ctn family of armadillo-related proteins that are essential for organizing the desmosomal plaque. Recent findings identified PKPs in stress granules, suggesting an association with the translational machinery. However, a role of PKPs in controlling translation remained elusive so far. In this study, we show a direct association of PKP1 with the eukaryotic translation initiation factor 4A1 (eIF4A1). PKP1 stimulated eIF4A1-dependent translation via messenger RNA cap and encephalomyocarditis virus internal ribosomal entry site (IRES) structures, whereas eIF4A1-independent translation via hepatitis C virus IRES was not affected. PKP1 copurified with eIF4A1 in the cap complex, and its overexpression stimulated eIF4A1 recruitment into cap-binding complexes. At the molecular level, PKP1 directly promoted eIF4A1 adenosine triphosphatase activity. The stimulation of translation upon PKP1 overexpression correlated with the up-regulation of proliferation and cell size. In conclusion, these findings identify PKP1 as a regulator of translation and proliferation via modulation of eIF4A1 activity and suggest that PKP1 controls cell growth in physiological and pathological conditions. |
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