Increased expression of eukaryotic translation initiation factors eIF-4E and eIF-2 alpha in response to growth induction by c-myc.

作者：Igor B. Rosenwald, David B. Rhoads, Larry Callanan, Kurt J. Isselbacher, Emmett V. Schmidt · 发表于：Proceedings of the National Academy of Sciences · 年份：1993 · DOI：10.1073/pnas.90.13.6175 · 被引用次数：255 · 研究领域：RNA and protein synthesis mechanisms、RNA Research and Splicing、RNA modifications and cancer

Although activation of c-myc is a critical step in the development of lymphomas and other tumors, its normal function(s) in cell growth remain obscure because few myc-regulated genes are known. myc expression normally increases in response to mitogens and peaks in G1 when additional protein synthesis is required for cell-cycle progression. Protein synthesis is controlled by the availability of translation initiation factors, including the mRNA cap binding protein (eIF-4E) and the alpha subunit of the eIF-2 complex that binds the initiator Met-tRNA. Consequently we examined eIF-4E and eIF-2 alpha for evidence of regulation by c-myc. Expression of eIF-4E and eIF-2 alpha correlated with c-myc expression in fibroblasts after growth stimulation. In addition, expression of eIF-4E and eIF-2 alpha was increased in myc-transformed rat embryo fibroblasts but was not increased in ras-transformed cells. Transcription rates of eIF-4E and eIF-2 alpha mRNAs were regulated by c-myc in cells expressing an estrogen receptor-Myc fusion protein. Finally, electrophoretic mobility-shift assays identified a sequence element in the eIF-2 alpha promoter, TCCGCAT-GCGCG, which was specifically retarded by extracts of myc-expressing cells. c-myc is thought to deregulate the growth of cancer cells by activating transcription, suggesting that specific genes regulated by c-myc should also function as oncogenes. In previous studies these translation initiation factors could induce neoplastic growth because ...