PMID:10400710

Citation	Zimmermann, H, Degenkolbe, R, Bernard, HU and O'Connor, MJ (1999) The human papillomavirus type 16 E6 oncoprotein can down-regulate p53 activity by targeting the transcriptional coactivator CBP/p300. J. Virol. 73:6209-19
Abstract	The transforming proteins of the small DNA tumor viruses, simian virus 40 (SV40), adenovirus, and human papillomavirus (HPV) target a number of identical cellular regulators whose functional abrogation is required for transformation. However, while both adenovirus E1A and SV40 large T transforming properties also depend on the targeting of the transcriptional coactivator CBP/p300, no such interaction has been described for the HPV oncoprotein E6 or E7. Here, we demonstrate that the HPV-16 E6 protein, previously shown to facilitate the degradation of p53 in a complex with E6-associated protein (E6AP), also targets CBP/p300 in an interaction involving the C-terminal zinc finger of E6 and CBP residues 1808 to 1826. Furthermore, this interaction is limited to E6 proteins of high-risk HPVs associated with cervical cancer that have the capacity to repress p53-dependent transcription. An HPV-16 E6 mutant (L50G) that binds CBP/p300, but not E6AP, is still capable of down-regulating p53 transcriptional activity. Thus, HPV E6 proteins possess two distinct mechanisms by which to abrogate p53 function: the repression of p53 transcriptional activity by targeting the p53 coactivator CBP/p300, and the removal of cellular p53 protein through the proteosome degradation pathway.
Links	PubMed PMC112697
Keywords	Amino Acid Sequence; CREB-Binding Protein; Down-Regulation; HeLa Cells; Humans; Molecular Sequence Data; Nuclear Proteins/genetics; Nuclear Proteins/metabolism; Oncogene Proteins, Viral/genetics; Oncogene Proteins, Viral/metabolism; Papillomaviridae/metabolism; Repressor Proteins; Trans-Activators/genetics; Trans-Activators/metabolism; Transcription, Genetic; Tumor Suppressor Protein p53/metabolism
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Annotations

Gene product	Qualifier	GO Term	Evidence Code	with/from	Aspect	Extension	Notes	Status
HPV16:VE6		GO:0045892: negative regulation of transcription, DNA-dependent	ECO:0000315:		P		Figure 7. HPV-16 E6 represses the ability of CBP to activate p53-dependent transcription.	complete CACAO 8543
HPV16:VE6		GO:0039653: suppression by virus of host transcription	ECO:0000315:		P		Figure 7	complete CACAO 8571
HPV16:VE6	involved_in	GO:0039653: suppression by virus of host transcription	ECO:0000315: mutant phenotype evidence used in manual assertion		P		Seeded From UniProt	complete

References

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