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}
}
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… Expand
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. Expand
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. Expand
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. Expand
Degradation of p53 can be targeted by HPV E6 sequences distinct from those required for p53 binding and trans-activation
TLDR
It is shown that E 6 proteins of both oncogenic and benign HPV types associate in vitro with p53, but binding by E6 proteins of benign HPVtypes cannot target p53 for degradation, and a C-terminal region of E6 conserved among all HPV types is important for p53 binding. Expand
Cell transformation by the E7 oncoprotein of human papillomavirus type 16: interactions with nuclear and cytoplasmic target proteins.
TLDR
A review of available data on the interaction of E7 with cellular regulatory factors and functional consequences of these interactions focuses on a set of recently identified new target proteins for the E7 oncoprotein, which sheds new light on E7 functions required for cell transformation and immortalization. Expand
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. Expand
Degradation of p 53 by natural variants of the E 6 protein of human papillomavirus type 16
The degradation of p53 by high-risk human papillomavirus (HR-HPV) E6 proteins is recognized as necessary for the immortalization of mammary epithelial cells and the progression of cancer. The HR-HPVExpand
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. Expand
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. Expand
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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. Expand
The human papillomavirus type 16 E7 gene encodes transactivation and transformation functions similar to those of adenovirus E1A
TLDR
Evidence is presented that the HPV-16 E7 open reading frame encodes transcriptional transactivation and cellular transformation functions analogous to those of adenovirus E1A proteins. Expand
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. Expand
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. Expand
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. Expand
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). Expand
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. Expand
HPV16 E6 and E7 proteins cooperate to immortalize human foreskin keratinocytes.
TLDR
It is concluded that HPV16 E6 and E7 cooperative to immortalize human keratinocytes in vitro with an efficiency similar to that of the entire early region of the viral DNA. Expand
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. Expand
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. Expand
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