The adenovirus E4orf6 E3 ubiquitin ligase complex assembles in a novel fashion.
The human adenovirus E4orf6 and E1B55K proteins are part of an E3 ubiquitin ligase complex that degrades p53, Mre11 and probably other cellular polypeptides. Our group has demonstrated previously that this complex contains Cul5, Rbx1 and Elongin B and C and is formed through interactions of these cellular proteins with E4orf6. Although this E4orf6 complex is similar in many ways to the cellular SCF and VBC E3 ligase complexes, our previous work indicated that unlike all known Cullin-containing complexes, E4orf6 contains two functional BC-box motifs that permit interactions with Elongin B and C. Here we show that a third BC-box exists that also appears to be fully functional. In addition, we attempted to identify a region in E4orf6 responsible for the specific selection of Cul5, which we show herein by knocking down Cul5 protein levels, is essential for p53 degradation. One sequence within E4orf6 shares limited homology with the 'Cul5 box motif', a recently identified sequence found to be responsible for selection of Cul5 in some cellular Cullin-containing E3 ligase complexes; however, genetic analysis indicated that this motif is not involved in Cullin binding or p53 degradation. Thus E4orf6 appears to utilize a different mechanism for Cul5 selection, and, both in terms of interactions with Elongin B and C and with Cul5, assembles the E3 ligase complex in a highly novel fashion.
Cheng
Chi Ying
CY
Department of Biochemistry, McGill University, McIntyre Medical Building, 3655 Promenade Sir William Osler, Montreal, Quebec, Canada H3G 1Y6.
Blanchette
Paola
P
Branton
Philip E
PE
D017504:Adenovirus E4 Proteins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D000260:Adenoviruses, Human / Q000201:enzymology* / Q000235:genetics; D020816:Amino Acid Motifs; D000595:Amino Acid Sequence; D001483:Base Sequence; D002460:Cell Line; D004279:DNA, Viral / Q000235:genetics; D005814:Genes, Viral; D006801:Humans; D008969:Molecular Sequence Data; D046912:Multiprotein Complexes; D016366:Open Reading Frames; D010957:Plasmids / Q000235:genetics; D011994:Recombinant Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D014162:Transfection; D043743:Ubiquitin-Protein Ligase Complexes / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D044767:Ubiquitin-Protein Ligases / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism
D017504:Adenovirus E4 Proteins; D004279:DNA, Viral; D046912:Multiprotein Complexes; D011994:Recombinant Proteins; D043743:Ubiquitin-Protein Ligase Complexes; D044767:Ubiquitin-Protein Ligases