The interplay between SUMOylation and phosphorylation of PKC delta facilitates oxidative stress-induced apoptosis

Although the increase in the number of identified posttranslational modifications (PTMs) has substantially improved our knowledge about substrate site specificity of single PTMs, the fact that different types of PTMs can crosstalk and act in concert to exert important regulatory mechanisms for protein function has not gained much attention. Here, we show that protein kinase C delta (PKC delta) is SUMOylated at lysine 473 in its C-terminal catalytic domain, and the SUMOylation increases PKC delta stability by repressing its ubiquitination. In addition, we uncover a functional interplay between the phosphorylation and SUMOylation of PKC delta, which can strengthen each other through recruiting SUMO E2/E3 ligases and the PKC delta kinase, respectively, to the PKC delta complexes. We identified PIAS2 beta as the SUMO E3 ligase of PKC delta. More importantly, by enhancing PKC delta protein stability and its phosphorylation through an interdependent interplay of the PTMs, the SUMOylation of PKC delta promotes apoptotic cell death induced by H2O2. We conclude that SUMOylation represents an important regulatory mechanism of PKC delta PTMs for the kinase's function in oxidative cell damage.