Phosphorylation by p44 MAP kinase/ERK1 stimulates CBP histone acetyl transferase activity in vitro

The transcriptional coactivator CBP displays an intrinsic histone acetyl tr ansferase (HAT) activity which seems to participate in transcriptional acti vation through the destabilization of nucleosome structure. CBP is involved in the activity of several transcription factors that are nuclear endpoint s of intracellular signal transduction pathways. In some instances, the tra nscription factors are phosphorylated upon cell activation, which induces t heir interaction with CBP. CBP itself is a phosphoprotein and can be phosph orylated by cycle-dependent kinases or by MAP kinases, Here we show that CB P phosphorylation by p44 MAP kinase/ERK1 results in the stimulation of its HAT enzymatic activity. The p44 MAP kinase/ERK1 phosphorylation sites are l ocated in the C-terminal part of the protein, outside of the HAT domain. Th ese sites are required for enzymatic stimulation, suggesting that phosphory lation by p44 MAP kinase/ERK1 induces a conformational change of the CBP mo lecule, Our data suggest that, in some instances, CBP itself might be a tar get for signal transduction pathways, (C) 1999 Academic Press.