In quiescent cells that have withdrawn from the cell cycle, protein translation is generally depressed by virtue of inhibition of the activity of the cap-dependent translation factor, eukaryotic initiation factor eIF4. One exception is the cyclin-dependent kinase inhibitor p27, which has high rates of expression in quiescent cells. Through analysis of the translation of a reporter from a bicistronic mRNA containing the p27 5′ untranslated region (UTR), Miskimins et al. show that p27 contains an internal ribosome entry sequence. In proliferating cells, the expression of an epitope-tagged p27 from the complete 5′ UTR was low, but could be stimulated by treatment with a drug to induce withdrawal from the cell cycle. In cells expressing a construct lacking the complete 5′ UTR, expression was high in both proliferating and quiescent cells. Thus, translation from the internal ribosome entry sequence can be regulated and provides a mechanism by which proteins can be differentially upregulated despite inhibition of cap-dependent translation.
W. K. Miskimins, G. Wang, M. Hawkinson, R. Miskimins, Control of cyclin-dependent kinase inhibitor p27 expression by cap-independent translation. Mol. Cell. Biol. 21, 4960-4967 (2001). [Abstract] [Full Text]