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Comment |
Urban RJ, et al reported that Protein Kinase C Iota Enhances the Transcriptional Activity of the Porcine P450 Side Chain Cleavage Insulin-like Response Element.
IGF-I enhances steroidogenesis in granulosa cells by stimulating the expression of the rate-limiting steroidogenic enzyme, cytochrome P450 side-chain cleavage (P450scc). This effect is mediated through an IGF response element (IGFRE) that binds polypyrimidine tract-binding protein (PTB)-associated splicing factor (PSF) and Sp1. Sp1 is essential for activation of the IGFRE while PSF functions as a repressor. Urban RJ, et al investigated mechanisms of modulation of the IGFRE by the atypical protein kinase C, PKC iota, in a porcine stable granulosa cell line, JC-410. PKC iota was found in nuclear extracts and levels were increased by IGF-I after 24 and 48 h of treatment. Immunoprecipitation experiments demonstrated that PSF and PKC iota associated with each other in nuclear extracts from JC-410 cells. Transient transfection with expression plasmids of kinase-active and kinase-deficient PKC iota isoforms enhanced transcriptional activity of the IGFRE regardless of kinase catalytic activity. Depletion of PKC iota protein by siRNA suppressed basal IGFRE activity, but did not prevent IGF-I stimulation of the IGFRE. We conclude that PKC iota enhances transcriptional activity of the porcine P450scc IGFRE independent of kinase activity by a mechanism involving protein-protein interaction with PSF.
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