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

@article{Scheffner1990TheEO,
  title={The E6 oncoprotein encoded by human papillomavirus types 16 and 18 promotes the degradation of p53},
  author={Martin Scheffner and Bruce A. Werness and Jon M. Huibregtse and Arnold J. Levine and Peter M. Howley},
  journal={Cell},
  year={1990},
  volume={63},
  pages={1129-1136}
}
Interaction of the human papillomavirus type 16 E6 oncoprotein with wild-type and mutant human p53 proteins
TLDR
No requirement for destabilizing amino acids at the N terminus of p53 was found, nor was evidence found that HPV-16 E6 could provide this determinant in trans, indicating that the N-terminal rule pathway is not involved in the E6-promoted degradation of p 53.
Degradation of p53 by natural variants of the E6 protein of human papillomavirus type 16.
TLDR
It is demonstrated that both the D25E and L83V variants downregulate p53 through a ubiquitin-proteasome pathway, and that the effect is very similar to that of the prototype E6 protein.
Degradation of p53 only is not sufficient for the growth stimulatory effect of human papillomavirus 16 E6 oncoprotein in human embryonic fibroblasts
TLDR
Results show that the E6 gene stimulates growth of HEF cells, but that this activity involves some other E 6 gene‐mediated functions than degradation of the p53 protein.
The E6 Oncoproteins of High-Risk Papillomaviruses Bind to a Novel Putative GAP Protein, E6TP1, and Target It for Degradation
TLDR
Using the yeast two-hybrid system, a novel E6-binding protein is isolated, designated E6TP1 (E6-targeted protein 1), which exhibits high homology to GTPase-activating proteins for Rap, including SPA-1, tuberin, and Rap1GAP and is a potential link between HPV E6 oncogenesis and alteration of a small G protein signaling pathway.
The E7 Oncoprotein of Human Papillomavirus Type 16 Stabilizes p53 through a Mechanism Independent of p19ARF
TLDR
It is shown that E7 stabilizes p53 in mouse embryo fibroblasts lacking p19ARF, indicating that in addition to inhibiting the ability of MDM2 to regulate p53, E7 must block signaling steps downstream of p53 to allow cell division.
Degradation of p 53 by natural variants of the E 6 protein of human papillomavirus type 16
TLDR
It is demonstrated that both the D25E and L83V variants downregulate p53 through a ubiquitinproteasome pathway, and that the effect is very similar to that of the prototype E6 protein.
The Human Papillomavirus E7 Oncoprotein Functionally Interacts with the S4 Subunit of the 26 S Proteasome*
TLDR
A human placenta cDNA library was screened by yeast two-hybrid assay using HPV 16 E7 as a bait and the subunit 4 (S4) ATPase of the 26 S proteasome was identified as a novel E7-binding protein.
Stabilization and functional impairment of the tumor suppressor p53 by the human papillomavirus type 16 E7 oncoprotein.
TLDR
The results suggest that E7 can interfere with the normal turnover of p53 but that the resulting increase of p 53 has no detectable transcriptional consequences on the p53 targets that the authors investigated.
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References

SHOWING 1-10 OF 54 REFERENCES
Association of human papillomavirus types 16 and 18 E6 proteins with p53.
TLDR
This study shows that the E6 protein of HPV-16 is capable of binding to the cellular p53 protein, providing further evidence that the human papillomaviruses, the adenovirus type 5, and SV40 may effect similar cellular pathways in transformation.
The human papilloma virus-16 E7 oncoprotein is able to bind to the retinoblastoma gene product.
TLDR
The results suggest that these three DNA viruses may utilize similar mechanisms in transformation and implicate RB binding as a possible step in human papilloma virus-associated carcinogenesis.
The E7 open reading frame of human papillomavirus type 16 encodes a transforming gene.
TLDR
Mutational analysis of the E6/E7 plasmid indicated that E7 was the gene primarily responsible for inducing anchorage independent growth, which represents a third class of PV transforming gene and correlates with E7 being selectively retained and expressed in HPV associated cervical carcinomas and cell lines.
Identification of human papillomavirus type 18 transforming genes in immortalized and primary cells
TLDR
It is found that in immortalized fibroblasts, both E6 and E7 (but not E6*) are capable of inducing anchorage-independent growth, and the development of human cervical carcinomas may involve a series of steps involving multiple viral and cellular gene products.
Complex formation of human papillomavirus E7 proteins with the retinoblastoma tumor suppressor gene product.
TLDR
The E7 proteins encoded by the human papillomaviruses associated with anogenital lesions share significant amino acid sequence homology and were assessed for their ability to form complexes with the retinoblastoma tumor suppressor gene product (p105‐RB).
The E6 and E7 genes of the human papillomavirus type 16 together are necessary and sufficient for transformation of primary human keratinocytes
TLDR
Both the full-length E6 and E7 genes were required for the induction of keratinocyte immortalization and resistance to terminal differentiation and mutation of either gene in the context of this recombinant plasmid eliminated the ability to induce stable differentiation-resistant transformants.
Transcriptional activation by the papillomavirus E6 zinc finger oncoprotein.
TLDR
Data demonstrated that the BPV E6 gene encodes a transcription activation domain and imply that a specific structure of the protein, most likely the zinc fingers, is critical for this function, and may be required for its oncogenic activity.
Human papillomavirus type 16 transformation of primary human embryonic fibroblasts requires expression of open reading frames E6 and E7
TLDR
It was concluded that HPV-16 transformation (extension of the life span) of human fibroblasts requires expression of genes E6 and E7.
Comparison of the in vitro transforming activities of human papillomavirus types.
TLDR
It is demonstrated that the E7 gene of HPV16 by itself is sufficient to co‐operate with activated ras to produce transformed cells which are tumorigenic in immunocompetent animals.
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