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PKCzetaII is a target for degradation through the tumour suppressor protein pVHL

Xavier Iturrioz1, Peter J Parker

  • 1Protein Phosphorylation Laboratory, Cancer Research UK, London Research Institute, 44 Lincoln's Inn Fields Laboratories, London WC2A 3PX, UK.

FEBS Letters
|March 14, 2007
PubMed

Insights

The Von Hippel-Lindau protein (pVHL) targets PKCzetaII for degradation, a variant that hinders epithelial cell polarization. This interaction, mediated by specific protein domains, involves ubiquitination and proteasomal breakdown of PKCzetaII.

Area of Science:

  • Cell Biology
  • Molecular Biology
  • Cancer Research

Background:

  • Protein kinase C zeta (PKCzeta) has variants, including PKCzetaII, which is rapidly degraded and inhibits epithelial cell polarization.
  • The Von Hippel-Lindau protein (pVHL) is an E3 ligase and tumor suppressor involved in protein degradation pathways.

Purpose of the Study:

  • To investigate the interaction between PKCzetaII and pVHL.
  • To elucidate the molecular mechanisms underlying PKCzetaII degradation by pVHL.

Main Methods:

  • Deletion studies of PKCzetaII and pVHL to identify interacting domains.
  • Analysis of ubiquitination and proteasomal degradation pathways.

Main Results:

  • PKCzetaII is a direct target for pVHL-mediated degradation.
  • The N-terminal PB1 domain of PKCzetaII is crucial for pVHL complex formation.
  • The C-terminal region of PKCzetaII is essential for pVHL and proteasome-dependent turnover.
  • The pVHL effector domain is the primary binding site for PKCzetaII.

Conclusions:

  • pVHL recruits PKCzetaII through its PB1 domain.
  • pVHL induces ubiquitination and degradation of PKCzetaII via its C-terminus.
  • This mechanism highlights a novel role for pVHL in regulating PKCzetaII stability and epithelial cell polarization.

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