The human papillomavirus type 16 E6 oncoprotein can down-regulate p53 activity by targeting the transcriptional coactivator CBP/p300.

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.

journal_name

J Virol

journal_title

Journal of virology

authors

Zimmermann H,Degenkolbe R,Bernard HU,O'Connor MJ

doi

10.1128/JVI.73.8.6209-6219.1999

subject

Has Abstract

pub_date

1999-08-01 00:00:00

pages

6209-19

issue

8

eissn

0022-538X

issn

1098-5514

journal_volume

73

pub_type

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