Molecular interaction between human tumor marker protein p150, the largest subunit of eIF3, and intermediate filament protein K7.
The human tumor marker protein p150 was identified as the largest subunit of eukaryotic translation initiation factor 3 (eIF3) (also known as p170/p180). Its expression level is not only upregulated in many transformed cell lines, but also in several human cancers including breast, cervical, esophageal, and stomach carcinomas. The function of p150 in cancer and initiation of translation are not well understood. Using the yeast two-hybrid genetic screen, we found that a portion of p150 interacts with hPrt1, another subunit of eIF3, and cytokeratin 7, an intermediate filament protein. The interactions between p150 and hPrt1, and between p150 and cytokeratin 7 were verified both in vivo and in vitro. The interaction site for hPrt1 was mapped to the carboxyl half of the coiled-coil region of the p150 protein between amino acids 664-835. The expression of hPrt1 was clearly upregulated in cancer tissue, similarly to that of p150. By contrast, no substantial difference in the expression level of cytokeratin 7 was observed between cancer and normal breast tissue, suggesting that cytokeratin 7 expression is not co-regulated with p150. Taken together, our studies suggest a new role for p150 in translation initiation, possibly by acting as an adapter molecule between the translation initiation apparatus and the cytoskeleton structure in the cell.
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Friedrich Miescher Institute, Novartis Research Foundation, CH-4002 Basel, Switzerland.
Holbro
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Alonso
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Gerosa
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Burger
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D001665:Binding Sites; D015153:Blotting, Western; D001940:Breast / Q000378:metabolism; D001943:Breast Neoplasms / Q000378:metabolism; D002846:Chromatography, Affinity; D003598:Cytoskeletal Proteins / Q000737:chemistry / Q000378:metabolism* / Q000502:physiology; D003599:Cytoskeleton / Q000378:metabolism; D018076:DNA, Complementary / Q000378:metabolism; D039621:Eukaryotic Initiation Factor-3; D005260:Female; D015723:Gene Library; D005982:Glutathione Transferase / Q000378:metabolism; D006367:HeLa Cells; D006801:Humans; D015151:Immunoblotting; D053552:Keratin-7; D007633:Keratins / Q000737:chemistry / Q000378:metabolism*; D010448:Peptide Initiation Factors / Q000737:chemistry / Q000378:metabolism*; D011233:Precipitin Tests; D039665:Prokaryotic Initiation Factor-3; D011485:Protein Binding; D014176:Protein Biosynthesis; D017434:Protein Structure, Tertiary; D011993:Recombinant Fusion Proteins / Q000737:chemistry; D014407:Tumor Cells, Cultured; D020798:Two-Hybrid System Techniques; D015854:Up-Regulation
D003598:Cytoskeletal Proteins; D018076:DNA, Complementary; C105988:EIF3A protein, human; D039621:Eukaryotic Initiation Factor-3; C507497:KRT7 protein, human; D053552:Keratin-7; D010448:Peptide Initiation Factors; D039665:Prokaryotic Initiation Factor-3; D011993:Recombinant Fusion Proteins; D007633:Keratins; D005982:Glutathione Transferase