The role of c-myc in regulation of translation initiation

Abstract

Translation initiation is important for the regulation of both cell growth and cell division. It is uniquely poised to coordinate overall cell proliferation by its effects on both growth and division. A number of translation initiation factors are transcriptional targets of c-myc in a variety of assays. In particular, the mRNA cap-binding protein eIF4E has a myc-binding sequence in its promoter that is myc responsive in reporter assays and contains a highaffinity myc-binding site in chromosome immunoprecipitation experiments. Several differential expression screens have demonstrated altered levels of eIF4E, along with several other translation initiation factors, in response to alterations of c-myc levels. The potential for eIF4E and other translational control elements to mediate myc's transforming functions is particularly important because eIF4E is itself a known oncogenic factor. The ability of translation initiation factors to affect both cell division control and cell growth control coincides with myc's remarkable effects on both cell growth and cell division.

Rhythm changes of clock genes, apoptosis-related genes and atherosclerosis-related genes in apolipoprotein E knockout mice

“…c-Myc regulates cell growth and proliferation (24). c-Myc activation and target genes may have long-term effects on smooth muscle cell proliferation, which may contribute to the development of atherosclerotic lesions (25,26).…”

Mechanisms of translational deregulation in human tumors and therapeutic intervention strategies

“…Although less is known about how other commonly mutated oncogenes and tumor suppressors directly impact on translational regulation, it should be noted that myc increases the transcription of many ribosomal proteins, initiation factors, and rRNA ( Schmidt, 2004), and p53 inhibits rRNA transcription (Zhai and Comai, 2000). In addition, the levels of p53 itself are regulated by ribosomal proteins RPL5, RPL26 and RPL11 (Marechal et al, 1994;Takagi et al, 2005;Dai et al, 2006).…”

Controlling Gene Expression through RNA Regulons: The Role of the Eukaryotic Translation Initiation Factor eIF4E

“…One target, c-myc, is an export and translation target of eIF4E 3,7 and has also been reported to upregulate transcription of eIF4E. 39 This provides one, of likely many candidates, for providing feedback on the regulon. One would expect that master nodes in these networks would have conduits to interact efficiently with other nodes.…”