Direct interaction of the beta-domain of VHL tumor suppressor protein with the regulatory domain of atypical PKC isotypes.
VHL tumor suppressor protein contains two domains, alpha and beta. The alpha-domain is involved in the formation of a large protein complex suggested to be involved in ubiquitin-mediated protein degradation. However, the role of the beta-domain, which may recognize the target proteins for protein degradation, remains unknown. Here we report that the beta-domain interacts directly with atypical PKC isotypes, PKCzeta and PKClambda. Further, the regulatory domain of aPKC is sufficient for this direct protein-protein interaction. Since aPKC isotypes have been implicated in the regulation of cell growth and apoptosis, these results suggest that aPKC isotypes are potential direct target of the VHL beta-domain.
Okuda
H
H
Department of Urology, Kochi Medical School, Kochi, 783-8505, Japan.
Hirai
S
S
Takaki
Y
Y
Kamada
M
M
Baba
M
M
Sakai
N
N
Kishida
T
T
Kaneko
S
S
Yao
M
M
Ohno
S
S
Shuin
T
T
D000595:Amino Acid Sequence; D001665:Binding Sites; D002478:Cells, Cultured; D016147:Genes, Tumor Suppressor; D006801:Humans; D007527:Isoenzymes / Q000378:metabolism; D007668:Kidney / Q000166:cytology; D008025:Ligases; D008969:Molecular Sequence Data; D010446:Peptide Fragments / Q000235:genetics / Q000378:metabolism; D011233:Precipitin Tests; D011485:Protein Binding; D011493:Protein Kinase C / Q000235:genetics / Q000378:metabolism*; D011506:Proteins / Q000235:genetics / Q000378:metabolism*; D011994:Recombinant Proteins / Q000378:metabolism; D025521:Tumor Suppressor Proteins; D044767:Ubiquitin-Protein Ligases; D051794:Von Hippel-Lindau Tumor Suppressor Protein; D000099221:Protein Kinase C zeta
D007527:Isoenzymes; D008025:Ligases; D010446:Peptide Fragments; D011493:Protein Kinase C; D011506:Proteins; D011994:Recombinant Proteins; D025521:Tumor Suppressor Proteins; D044767:Ubiquitin-Protein Ligases; D051794:Von Hippel-Lindau Tumor Suppressor Protein; D000099221:Protein Kinase C zeta; C087857:protein kinase C gamma; C497446:VHL protein, human