Your browser version may not work well with NCBI's Web applications. More information here...
1: J Biol Chem. 2001 Nov 23;276(47):43611-7. Epub 2001 Sep 26.
Related Articles, Links
Click here to read Click here to read
The von Hippel-Lindau tumor suppressor protein mediates ubiquitination of activated atypical protein kinase C.

Okuda H, Saitoh K, Hirai S, Iwai K, Takaki Y, Baba M, Minato N, Ohno S, Shuin T.

Department of Urology, Kochi Medical School, Kochi 783-8505, Japan.

The von Hippel-Lindau tumor-suppressor protein (pVHL) forms a protein complex (VCB-Cul2) with elongin C, elongin B, Cul-2, and Rbx1, which functions as a ubiquitin-protein ligase (E3). The alpha-subunits of the hypoxia-inducible factors have been identified as targets for the VCB-Cul2 ubiquitin ligase. However, a variety of cellular defects caused by the depletion of pVHL cannot be explained solely by the ubiquitin-mediated degradation of hypoxia-inducible factor-alpha. We show here that a member of the atypical protein kinase C (PKC) group, PKClambda, is ubiquitinated by the pVHL-containing E3 enzyme. An active PKClambda mutant is ubiquitinated more extensively than wild-type PKClambda in HEK293 cells, and the ubiquitination is further enhanced by the overexpression of pVHL. The activation of wild-type PKClambda by serum stimulation of cells enhances the ubiquitination of the protein, supporting the notion that active PKClambda is preferentially ubiquitinated by VCB-Cul2 ubiquitin ligase. Furthermore, we show that PKClambda can be ubiquitinated in vitro in a cell-free ubiquitination assay using purified recombinant components including VCB-Cul2. Given the known function of aPKC in the regulation of cell polarity and cell growth, PKClambda may be a target of pVHL in its function as a tumor suppressor.

PMID: 11574546 [PubMed - indexed for MEDLINE]