Inhibition of histone acetyltransferase function of p300 by PKCdelta.

Protein kinase Cdelta (PKCdelta) is one of the functionally distinct isoforms in PKC family. p300 is a histone acetyltransferase/transcription coactivator. They share certain properties, such as ubiquitous expression, growth and tumor suppression, and ability to enhance differentiation and apoptosis. In this study, we found that PKCdelta but not classical PKC, specifically phosphorylates p300 at serine 89 in vitro and in vivo. This phosphorylation causes inhibition of p300 intrinsic HAT activity. Subsequently, the targeted acetylation of nucleosomal histones is markedly reduced, which causes repression of p300 transcription coactivator function. These findings identify a new signal transduction pathway by which PKCdelta may inhibit cell growth and promote cellular differentiation.