Phosphorylation of Tat-interactive protein 60 kDa by protein kinase Cε is important for its subcellular localisation

Abstract

Tat-interactive protein 60kDa is a nuclear acetyltransferase that both coactivates and corepresses transcription factors and has a definitive function in the DNA damage response. Here, we provide evidence that Tat-interactive protein 60kDa is phosphorylated by protein kinase Cɛ. In vitro, protein kinase Cɛ phosphorylates Tat-interactive protein 60kDa on at least two sites within the acetyltransferase domain. In whole cells, activation of protein kinase C increases the levels of phosphorylated Tat-interactive protein 60kDa and the interaction of Tat-interactive protein 60kDa with protein kinase Cɛ. A phosphomimetic mutant Tat-interactive protein 60kDa has distinct subcellular localisation compared to the wild-type protein in whole cells. Taken together, these findings suggest that the protein kinase Cɛ phosphorylation sites on Tat-interactive protein 60kDa are important for its subcelullar localisation. Regulation of the subcellular localisation of Tat-interactive protein 60kDa via phosphorylation provides a novel means of controlling Tat-interactive protein 60kDa function.