PKCzetaII is a target for degradation through the tumour suppressor protein pVHL.
PKCzetaII is a rapidly degraded variant of PKCzeta that suppresses epithelial cell polarisation. It is shown here that PKCzetaII is a target for the E3 ligase and tumour suppressor Von Hippel-Lindau protein (pVHL). Deletion studies demonstrate that the C-terminal region is required for the pVHL and proteasome dependent turnover of PKCzetaII, however it is the N-terminal PB1 domain of PKCzetaII that is required for pVHL complex formation. Reciprocal deletion studies define the pVHL effector domain as the dominant PKCzetaII binding site. The results indicate that pVHL recruits PKCzetaII via its PB1 domain and causes ubiquitination and degradation via the distal C-terminus of PKCzetaII.
Iturrioz
Xavier
X
Protein Phosphorylation Laboratory, Cancer Research UK, London Research Institute, 44 Lincoln's Inn Fields Laboratories, London WC2A 3PX, UK.
Parker
Peter J
PJ
D000818:Animals; D051379:Mice; D046988:Proteasome Endopeptidase Complex / Q000378:metabolism; D011493:Protein Kinase C / Q000235:genetics / Q000378:metabolism*; D017434:Protein Structure, Tertiary; D017384:Sequence Deletion; D025801:Ubiquitin / Q000378:metabolism; D044767:Ubiquitin-Protein Ligases / Q000378:metabolism*; D051794:Von Hippel-Lindau Tumor Suppressor Protein / Q000378:metabolism*
D025801:Ubiquitin; D044767:Ubiquitin-Protein Ligases; D051794:Von Hippel-Lindau Tumor Suppressor Protein; C488488:protein kinase C zeta II, mouse; D011493:Protein Kinase C; D046988:Proteasome Endopeptidase Complex