Plakophilin 1 stimulates translation by promoting eIF4A1 activity.
Plakophilins 1-3 (PKP1-3) are desmosomal proteins of the p120(ctn) 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.
Division of Pathobiochemistry, Martin Luther University Halle-Wittenberg, 06097 Halle, Germany.
Annika
A
Wolf
Malgorzata
M
Krause-Gruszczynska
Olaf
O
Birkenmeier
Antje
A
Ostareck-Lederer
Stefan
S
Hüttelmaier
Mechthild
M
Hatzfeld
D000251:Adenosine Triphosphatases / Q000378:metabolism; D002460:Cell Line; D049109:Cell Proliferation; D048429:Cell Size; D039601:Eukaryotic Initiation Factor-4A / Q000378:metabolism*; D006801:Humans; D051191:Plakophilins / Q000378:metabolism*; D011485:Protein Binding; D014176:Protein Biosynthesis; D021381:Protein Transport; D012314:RNA Cap Analogs / Q000378:metabolism; D012315:RNA Caps / Q000378:metabolism; D034741:RNA, Small Interfering / Q000378:metabolism; D022142:Secretory Vesicles / Q000378:metabolism
D051191:Plakophilins; D012314:RNA Cap Analogs; D012315:RNA Caps; D034741:RNA, Small Interfering; C017516:7-methylguanosine triphosphate; D039601:Eukaryotic Initiation Factor-4A; D000251:Adenosine Triphosphatases