Alternatively spliced HPV-18 E6* protein inhibits E6 mediated degradation of p53 and suppresses transformed cell growth.

Abstract:

:The E6 proteins originating from the tumour-associated Human Papillomavirus (HPV) types 16 and 18 have been shown to bind to and target the tumour suppressor protein, p53, for ubiquitin-mediated degradation. However, in cell lines derived from cervical neoplasias, the predominant early region transcripts are spliced and encode truncated forms of E6, termed E6*. We report here that HPV-18 E6* protein will interact both with the full-length E6 proteins from HPV-16 and HPV-18 and also with E6-AP, and subsequently blocks the association of full length E6 protein with p53. We also show that, as a result of this block, E6* can inhibit E6-mediated degradation of p53 both in vitro and in vivo. The biological consequences of this are increased transcriptional activity on p53-responsive promoters and an inhibition of cell growth in cells transfected with E6*. This is the first report of a potential biological function for this polypeptide and may represent a means by which HPV is able to modulate the activity of the full-length E6 protein with respect to p53 during viral infection.

journal_name

Oncogene

journal_title

Oncogene

authors

Pim D,Massimi P,Banks L

doi

10.1038/sj.onc.1201202

subject

Has Abstract

pub_date

1997-07-17 00:00:00

pages

257-64

issue

3

eissn

0950-9232

issn

1476-5594

journal_volume

15

pub_type

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