Sequential posttranslational modifications regulate PKC degradation

Mol Biol Cell. 2016 Jan 15;27(2):410-20. doi: 10.1091/mbc.E15-09-0624. Epub 2015 Nov 12.

Abstract

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 PKCα stability via a sequential cascade of PTMs. We demonstrate that PKCα 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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • CHO Cells
  • Cells, Cultured
  • Cricetulus
  • Down-Regulation
  • HeLa Cells
  • Humans
  • Phosphorylation
  • Proteasome Endopeptidase Complex / metabolism*
  • Protein Kinase C-alpha / metabolism*
  • Protein Processing, Post-Translational*
  • Sumoylation
  • Ubiquitin
  • Ubiquitination

Substances

  • Ubiquitin
  • PRKCA protein, human
  • Protein Kinase C-alpha
  • Proteasome Endopeptidase Complex