The Translation Initiation Factor eIF3-p48 Subunit Is Encoded byint-6, a Site of Frequent Integration by the Mouse Mammary Tumor Virus Genome*
- From the Department of Biological Chemistry, School of Medicine, University of California, Davis, California 95616 and the§Department of Biochemistry, Case Western Reserve University, School of Medicine, Cleveland, Ohio 44106
Abstract
Translation initiation factor eIF3 is a large, multisubunit protein complex that plays a central role in the pathway of initiation by promoting the binding of both methionyl-tRNAiand mRNA to the 40S ribosomal subunit. As part of a broad effort to elucidate the structure of eIF3, we have cloned and sequenced the human cDNA encoding the 48-kDa subunit, 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 indicates that the mouse gene encoding eIF3-p48 had previously been identified and characterized by others asint-6. The int-6 gene is the site of frequent integration of mouse mammary tumor virus DNA into chromosomes, implicating the gene in the regulation of cell proliferation. In addition, it was shown elsewhere that the homologous humanint-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 account for oncogenesis caused by these two viruses.
Footnotes
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↵* This work was supported by National Institutes of Health Grants GM22135 (to J. W. B. H.) and GM26796 (to W. C. M.) from the U. S. Public Health Service.The costs of publication of this article were defrayed in part by the payment of page charges. The article must therefore be hereby marked “advertisement” in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.
The nucleotide sequence(s) reported in this paper has been submitted to the GenBank™/EMBL Data Bank with accession number(s) U54562 and U54563.
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↵‡ Supported by a post-doctoral fellowship from the Human Frontiers Science Program.
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↵¶ To whom correspondence should be addressed. Tel.: 916-752-3235; Fax: 916-752-3516; E-mail: jwhershey{at}ucdavis.edu.
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↵1 The abbreviations used are: MMTV, mouse mammary tumor virus; kb, kilobase pair; PCR, polymerase chain reaction; PAGE, polyacrylamide gel electrophoresis; EST, expressed sequence tag; bp, base pair(s).
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↵2 K. Asano, H.-P. Vornlocher, N. J. Richter-Cook, W. C. Merrick, A. G. Hinnebusch, and J. W. B. Hershey, submitted for publication.
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- Received June 30, 1997.
- Revision received July 21, 1997.
