The E6 oncoprotein encoded by human papillomavirus types 16 and 18 promotes the degradation of p53

doi:10.1016/0092-8674(90)90409-8

Cell

Volume 63, Issue 6, 21 December 1990, Pages 1129-1136

https://doi.org/10.1016/0092-8674(90)90409-8 Get rights and content

Abstract

The E6 protein encoded by the oncogenic human papillomavirus types 16 and 18 is one of two viral products expressed in HPV-associated cancers. E6 is an oncoprotein which cooperates with E7 to immortalize primary human keratinocytes. Insight into the mechanism by which E6 functions in oncogenesis is provided by the observation that the E6 protein encoded by HPV-16 and HPV-18 can complex the wild-type p53 protein in vitro. Wild-type p53 gene has tumor suppressor properties, and is a target for several of the oncoproteins encoded by DNA tumor viruses. In this study we demonstrate that the E6 proteins of the oncogenic HPVs that bind p53 stimulate the degradation of p53. The E6-promoted degradation of p53 is ATP dependent and involves the ubiquitin-dependent protease system. Selective degradation of cellular proteins such as p53 with negative regulatory functions provides a novel mechanism of action for dominant-acting oncoproteins.

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Cell

ArticleThe E6 oncoprotein encoded by human papillomavirus types 16 and 18 promotes the degradation of p53

Abstract

Trends Biochem. Sci.

Cell

Cell

Cell

J. Biol. Chem.

Virology

Cell

Cell

Cell

Cell

Cell

Chromosome 17 deletions and p53 gene mutations in colorectal carcinomas

Science

Suppression of human colorectal carcinoma cell growth by wild-type p53

Science

Identification of human papillomavirus type 18 transforming genes in immortalized and primary cells

J. Virol.

Heterogeneity of the human papillomavirus group

J. Virol.

The human papillomavirus-16 E7 oncoprotein is able to bind the retinoblastoma gene product

Science

Participation of p53 cellular tumour antigen in transformation of normal embryonic cells

Nature

Meth A fibrosarcoma cells express two transforming mutant p53 species

Oncogene

Wild-type p53 can inhibit oncogene-mediated focus formation

Presence of a potent transcription activating sequence in the p53 protein

Science

Prediction of similar transforming regions in simian virus 40 large T, adenovirus E1A, and myc oncoproteins

J. Virol.

Activating mutations for transformation by p53 produce a gene product that forms an hsc70-p53 complex with an altered half-life

Mol. Cell. Biol.

Inducible and constitutive enhancer domains in the noncoding region of human papillomavirus type 18

J. Virol.

HPV16 E6 and E7 proteins cooperate to immortalize human foreskin keratinocytes

EMBO J.

Mutation is required to activate the p53 gene for cooperation with the ras oncogene and transformation

J. Virol.

Cellular immortalization by a cDNA clone encoding the transformation-associated phosphoprotein p53

Nature

Cis-trans recognition and subunit-specific degradation of short-lived proteins

Nature

Article
The E6 oncoprotein encoded by human papillomavirus types 16 and 18 promotes the degradation of p53