Association of E6AP (UBE3A) with human papillomavirus type 11 E6 protein.
The cellular E3 ubiquitin ligase E6AP (UBE3A) interacts with the cancer-associated HPV E6 oncoproteins, where together with the viral E6 oncoprotein it binds and targets the degradation of the p53 tumor suppressor. We find that the HPV-11E6 protein also associates with E6AP in vivo, and thereby can target the degradation of an E6-associated protein. Mutation of an E6-binding LXXLL peptide motif on E6AP eliminated the association, revealing a common mode of interaction between high- and low-risk E6 proteins and E6AP. E6AP was required for the in vivo degradation of DLG1 by both HVP-18 E6 and a chimeric HPV-11E6. The common functional interaction of both cancer-associated and non-cancer-associated E6 proteins with E6AP establishes a common mechanism for E6 proteins trophic to mucosal squamous epithelium.
Brimer
Nicole
N
Department of Pathology, University of Virginia. P.O. Box 800904, Charlottesville, VA 22908, USA.
Lyons
Charles
C
Vande Pol
Scott B
SB
D048868:Adaptor Proteins, Signal Transducing / Q000378:metabolism; D000818:Animals; D002460:Cell Line; D000074288:Discs Large Homolog 1 Protein; D016147:Genes, Tumor Suppressor; D052140:Human papillomavirus 11 / Q000378:metabolism*; D008565:Membrane Proteins / Q000378:metabolism; D009856:Oncogene Proteins, Viral / Q000737:chemistry / Q000378:metabolism*; D017434:Protein Structure, Tertiary / Q000502:physiology; D044767:Ubiquitin-Protein Ligases / Q000235:genetics / Q000378:metabolism*
D048868:Adaptor Proteins, Signal Transducing; C513314:DLG1 protein, human; D000074288:Discs Large Homolog 1 Protein; C469553:E6 protein, Human papillomavirus type 11; D008565:Membrane Proteins; D009856:Oncogene Proteins, Viral; C471639:UBE3A protein, human; D044767:Ubiquitin-Protein Ligases