Internal ribosome entry in the myc gene family

• Main Author: Jopling, Catherine L.
• Published: University of Leicester 2001
• Subjects: 571.6
• Online Access: http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.696938

The proto-oncogene c-myc is encoded by a transcript in which the 5' UTR contains a potent internal ribosome entry segment (IRES). The N-myc gene shows considerable homology to c-myc and also possesses a 5' UTR that is long and structured. Thus, the potential for internal ribosome entry within this UTR was examined. N-myc was found to contain an IRES that was of comparable activity to that of c-myc in non-neuronal cells, but was specifically activated relative to the c-myc IRES in neuronal cells in which the N-myc transcription is expressed. Furthermore, the activity of the N-myc IRES was specifically inhibited during neuronal differentiation, when N-myc expression is reduced. The trans-acting factor requirements for N-myc IRES function were examined and a candidate protein was found, although not characterised. An IRES was also identified in the 5' UTR of the third well-studied member of the myc gene family, L-myc. An alternative form of the UTR exists in which an intron is retained, but it was not possible to draw any definite conclusions on the IRES activity of this UTR. Translation of both c- and N-myc mRNAs can occur by both cap-dependent and IRES-dependent mechanisms, so the existence of IRESs within these transcripts was intriguing. c-Myc protein levels were analysed during apoptosis and were maintained, despite the apoptotic inhibition of protein synthesis and the short half-life of c-Myc. The activity of the c-myc IRES was maintained during apoptosis and was responsible for this effect. The c-myc IRES was also shown to lie downstream of the p38 mitogen-activated protein kinase signalling pathway.