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Molecular and Cellular Biology, September 2002, p. 6089-6099, Vol. 22, No. 17
0270-7306/02/$04.00+0     DOI: 10.1128/MCB.22.17.6089-6099.2002
Copyright © 2002, American Society for Microbiology. All Rights Reserved.

The 5' Untranslated Region of Protein Kinase C Directs Translation by an Internal Ribosome Entry Segment That Is Most Active in Densely Growing Cells and during Apoptosis

Department of Biology, University of York, York YO10 5YW, United Kingdom,¹ Molecular Development Laboratory, Murdoch Childrens Research Institute, Royal Children's Hospital, Parkville, Victoria 3052, Australia²

Received 4 February 2002/ Returned for modification 13 March 2002/ Accepted 4 June 2002

Protein kinase C (PKC) is a member of the PKC family of phospholipid-dependent serine/threonine kinases and is involved in cell proliferation, apoptosis, and differentiation. Previous studies have suggested that different PKC isoforms might be translationally regulated. We report here that the 395-nt-long 5' untranslated region (5' UTR) of PKC is predicted to form very stable secondary structures with free energies (G values) of around -170 kcal/mol. The 5' UTR of PKC can significantly repress luciferase translation in rabbit reticulocyte lysate but does not repress luciferase translation in a number of transiently transfected cell lines. By using a bicistronic luciferase reporter, we show that the 5' UTR of PKC contains a functional internal ribosome entry segment (IRES). The activity of the PKC IRES is greatest in densely growing cells and during apoptosis, when total protein synthesis and levels of full-length eukaryotic initiation factor 4G are reduced. However, the IRES activity of the 5' UTR of PKC is not enhanced during serum starvation, another condition shown to inhibit cap-dependent translation, suggesting that its potency is dependent on specific cellular conditions. Accumulating data suggest that PKC has a function as proliferating cells reach high density and in early and later events of apoptosis. Our studies suggest a mechanism whereby PKC synthesis can be maintained under these conditions when cap-dependent translation is inhibited.

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