The Von Hippel-Lindau tumor-suppressor protein interaction with protein kinase C {delta}

Xavier Iturrioz , Joanne Durgan , Véronique Calleja , Banafshé Larijani , Heiwa Okuda , Richard H Whelan , Peter J Parker (1)

1 Protein Phosphorylation laboratory

The Von Hippel-Lindau tumor-suppressor protein (pVHL) forms a multi-protein complex (VCB-Cul2) with elongin C, elongin B, Cul-2, and Rbx1, acting as a ubiquitin-ligase (E3) and directing proteasome-dependent degradation of targeted proteins. The {alpha}-subunit of hypoxia-inducible factor (Hif1{alpha}) is the principal substrate for the VCB-Cul2, however other substrates such as atypical protein kinase C (aPKC) have been reported. In the present study we show by FRET analysis measured by Fluorescence Lifetime Imaging Microscopy that PKC{delta} and pVHL interact directly in cells. This occurs through the catalytic domain of PKC{delta} (432-508) which appears to interact with two regions of pVHL, residues 113-122 and 130-154. Despite this robust interaction, analysis of the PMA-induced proteasome-dependent degradation of PKC{delta} in different renal cell carcinoma lines (RCC4, UMRC2 and 786 O) shows no correlation between the degradation of PKC{delta} and the presence of an active pVHL. In contrast to aPKC, PKC{delta} is thus not a conventional substrate of the ubiquitin-ligase complex VCB-Cul2 and the observed interaction between these two proteins must underlie a distinct signaling output.

Mots clés: Life Sciences

Xavier Iturrioz, Joanne Durgan, Véronique Calleja, Banafshé Larijani, Heiwa Okuda, et al.. The Von Hippel-Lindau tumor-suppressor protein interaction with protein kinase C {delta}. Biochemical Journal, 2006, 397 (1), pp.109-120. ⟨10.1042/BJ20060354⟩. ⟨hal-00478548⟩