Morrish, B.C. and Rumsby, M.G. (2002) The 5 ' untranslated region of protein kinase C delta directs translation by an internal ribosome entry segment that is most active in densely growing cells and during apoptosis. Molecular and Cellular Biology. pp. 6089-6099. ISSN 0270-7306
Protein kinase Cdelta (PKCdelta) 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 PKCdelta is predicted to form very stable secondary structures with free energies (DeltaG values) of around -170 kcal/mol. The 5' UTR of PKCdelta 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 PKCdelta contains a functional internal ribosome entry segment (IRES). The activity of the PKCdelta 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 PKCdelta 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 PKCdelta has a function as proliferating cells reach high density and in early and later events of apoptosis. Our studies suggest a mechanism whereby PKCdelta synthesis can be maintained under these conditions when cap-dependent translation is inhibited.
|Copyright, Publisher and Additional Information:||Copyright © 2002 American Society for Microbiology|
|Institution:||The University of York|
|Academic Units:||The University of York > Biology (York)|
|Depositing User:||Sherpa Assistant|
|Date Deposited:||04 Mar 2005|
|Last Modified:||25 Apr 2015 15:30|