The HPV-16 E6 and E6-AP complex functions as a ubiquitin-protein ligase in the ubiquitination of p53

@article{Scheffner1993TheHE,
  title={The HPV-16 E6 and E6-AP complex functions as a ubiquitin-protein ligase in the ubiquitination of p53},
  author={Martin Scheffner and Jon M. Huibregtse and Richard David Vierstra and Peter M. Howley},
  journal={Cell},
  year={1993},
  volume={75},
  pages={495-505}
}

The Role of the Ubiquitin Ligase E6-AP in Human Papillomavirus E6-mediated Degradation of PDZ Domain-containing Proteins*

TLDR
The RNA interference technology and mouse embryo fibroblasts derived from E6-AP-deficient mice are used to obtain information about the identity of the ubiquitin ligase(s) involved in E 6-mediated degradation of Dlg and it is proposed that the proteolytic properties of human papillomavirus E6 proteins are mediated by interaction with E7-AP.

Regulation of the Human Papillomavirus Type 18 E6/E6AP Ubiquitin Ligase Complex by the HECT Domain-Containing Protein EDD

TLDR
These studies suggest that changes in the levels of EDD expression during different stages of the viral life cycle or during malignancy could have a profound effect upon the ability of E6 to target various substrates for proteolytic degradation and thereby directly influence the development of HPV-induced malignancies.

The Role of E6AP in the Regulation of p53 Protein Levels in Human Papillomavirus (HPV)-positive and HPV-negative Cells*

TLDR
Evidence is provided for the involvement of E6AP in E6-mediated p53 degradation in vivo and also indicates that E 6AP may not be involved in the regulation of p53 ubiquitination in the absence of E 6.

Human Papillomavirus Type 16 E6 Induces Self-Ubiquitination of the E6AP Ubiquitin-Protein Ligase

TLDR
It is demonstrated that an E6 mutant that is able to immortalize human mammary epithelial cells but is unable to degrade p53 retains its ability to bind and degrade E6 AP, raising the possibility that E6-mediated degradation of E6AP contributes to its abilityto transform mammalian cells.

Ubiquitination of the HPV Oncoprotein E6 Is Critical for E6/E6AP-Mediated p53 Degradation

TLDR
It is demonstrated that HPV E6 is ubiquitinated by E6AP in presence of p53, and the data suggest that the HPV oncogene E6 might be an optimal pharmacologic.

A family of proteins structurally and functionally related to the E6-AP ubiquitin-protein ligase.

TLDR
Data strongly suggest that the rat 100-kDa protein and RSP5, as well as the other E6-AP-related proteins, belong to a class of functionally related E3 ubiquitin-protein ligases, defined by a domain homologous to the E 6-AP carboxyl terminus (hect domain).

Mapping the interactome of HPV E6 and E7 oncoproteins with the ubiquitin‐proteasome system

TLDR
A strategy for the rapid identification of interactions between host or pathogen proteins and the human ubiquitination system is established and the identified UPS factors interacted with most of E7 proteins across different HPV types.

Identification of a novel telomerase repressor that interacts with the human papillomavirus type-16 E6/E6-AP complex.

TLDR
It is proposed that the induction of telomerase by the HPV-16 E6/E6-AP complex involves targeting of NFX1-91, a newly identified repressor of telomersase, for ubiquitination and degradation.

The role of the ubiquitin proteasome pathway in papillomavirus pathogenicity

TLDR
It is demonstrated that PDZ domain-containing cell polarity regulators and critical components of the ubiquitin proteasome pathway are common targets of evolutionarily diverse oncogenic mucosal papillomavirus, which suggests that these pathways represent essential steps in the viral life cycles and in these viruses’ ability to induce malignancy.

Stepwise multipolyubiquitination of p53 by the E6AP-E6 ubiquitin ligase complex

TLDR
It is suggested that p53 is multipolyubiquitinated with short chains by E6AP-E6, and the permissive distance for the movement of the C-lobe restricts the length of the chains in the E6 AP-E 6-p53 ternary complex.
...

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Localization of the E6-AP regions that direct human papillomavirus E6 binding, association with p53, and ubiquitination of associated proteins

TLDR
Functional domains of E6-AP involved in binding E6, association with p53, and ubiquitination of p53 are mapped and it is shown that E 6-AP sequences in addition to those required for formation of a stable ternary complex with E6 and p 53 are necessary to stimulate the ubiquitinated p53.

Cloning and expression of the cDNA for E6-AP, a protein that mediates the interaction of the human papillomavirus E6 oncoprotein with p53

TLDR
The purification of E6-AP and the cloning of its corresponding cDNA, which contains a novel open reading frame encoding 865 amino acids, is reported, suggesting a model by which E6 deregulates cell growth control by the elimination of the p53 tumor suppressor protein.

A cellular protein mediates association of p53 with the E6 oncoprotein of human papillomavirus types 16 or 18.

TLDR
The E6 protein of human papillomavirus types 16 and 18 (HPV‐16 and HPV‐18) can stably associate with the p53 protein in vitro and is a monomeric protein of approximately 100 kDa, whereas p53 association with the factor can be detected only in the presence of E6.

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.

Targeted degradation of the retinoblastoma protein by human papillomavirus E7‐E6 fusion proteins.

TLDR
E7‐E6 fusion proteins using the E6 proteins of HPV‐6 and HPV‐11 have the ability to promote the degradation of the retinoblastoma protein, indicating that the property to target associated proteins for degradation is shared by the anogenital specific HPV E 6 proteins.

Homologs of the essential ubiquitin conjugating enzymes UBC1, 4, and 5 in yeast are encoded by a multigene family in Arabidopsis thaliana.

TLDR
Cl cloning of five genes encoding E2(15kDa) from Arabidiopsis thaliana is described andalyses of genomic Southern blots are consistent with the existence of multiple members encoding this E2 subfamily.

Degradation of nuclear oncoproteins by the ubiquitin system in vitro.

TLDR
The relative sensitivity to degradation of various E1A mutants in vivo is also maintained in the cell-free system, suggesting that the ubiquitin pathway may play a role in the cellular degradation of these proteins as well.
...