Sequential posttranslational modifications regulate PKC degradation

Cross-talk among different types of posttranslational modifications (PTMs) has emerged as an important regulatory mechanism for protein function. Here we elucidate a mechanism that controls PKCa stability via a sequential cascade of PTMs. We demonstrate that PKCa dephosphorylation decreases its sumoylation, which in turn promotes its ubiquitination and ultimately enhances its degradation via the ubiquitin-proteasome pathway. These findings provide a molecular explanation for the activation-induced down-regulation of PKC proteins.