THE TRANSLATION INITIATION-FACTOR EIF3-P48 SUBUNIT IS ENCODED BY INT-6, A SITE OF FREQUENT INTEGRATION BY THE MOUSE MAMMARY-TUMOR VIRUS GENOME

Translation initiation factor eIF3 is a large, multisubunit protein co mplex that plays a central role in the pathway of initiation by promot ing the binding of both methionyl-tRNA(i) and mRNA to the 40S ribosoma l subunit. As part of a broad effort to elucidate the structure of eIF 3, we have cloned and sequenced the human cDNA encoding the 48-kDa sub unit, eIF3-p48. The recombinant protein comigrates with the authentic p48 subunit in purified eIF3 and coprecipitates with affinity-purified antibodies to the p170 subunit of eIF3. A search of the data base ind icates that the mouse gene encoding eIF3 p48 had previously been ident ified and characterized by others as int-6. The int-6 gene is the site of frequent integration of mouse mammary tumor virus DNA into chromos omes, implicating the gene in the regulation of cell proliferation. In addition, it was shown elsewhere that the homologous human int-6 gene product binds to the human T-cell leukemia virus type I Tax protein, leading to the translocation of Int-6 to the cytoplasm. We discuss how the cytosolic function of eIF3-p48 (Int-6) in protein synthesis may a ccount for oncogenesis caused by these two viruses.