CoChat
Sign Up
Cited by 2,054

The DOI matches its Crossref record; 4 of the 4 references it cites were found in a registry or an index.

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

Scheffner, Martin, Huibregtse, Jon M., Vierstra, Richard D., Howley, Peter M.·1993·Cell
DOI 10.1016/0092-8674(93)90384-3
Open this paper in CoChat — free account

Abstract

The ubiquitin-dependent proteolytic pathway plays a major role in selective protein degradation. Ubiquitination of proteins requires the sequential action of the ubiquitin-activating enzyme (E1), ubiquitin-conjugating enzymes (E2), and in some cases ubiquitin-protein ligases (E3s). The oncogenic human papillomavirus (HPV) types 16 and 18 utilize this cellular proteolytic system to target the tumor suppressor protein p53. The HPV E6 oncoprotein binds to a cellular protein of 100 kd, termed E6-associated protein (E6-AP). The E6-E6-AP complex specifically interacts with p53, resulting in the rapid ubiquitin-dependent degradation of p53. Here we report the purification and identification of the factors necessary for the E6-E6-AP-mediated ubiquitination of p53. The ubiquitination of p53 requires the E1 enzyme and a novel E2 in mammalian cells, while E3 activity is conferred by the E6-E6-AP complex. Furthermore, E6-AP appears to have ubiquitin-protein ligase activity in the absence of E6.

Overview

Integrity signals

Registry

Crossref · 10.1016/0092-8674(93)90384-3

Cites

4 of 4 references verified0 citation errors · 0 not checkable

Statistics

Recomputing p-values needs the paper’s full text.

Verification

Claims the paper makes

This paper’s full text isn’t openly available, so its claims and self-check weren’t run. The registry and citation checks still apply.

Claims other papers make about this one

Each is checked against this paper’s own text: does it say what the citing paper says it does?

Citations

Cites

Show all 4 references

Research works printed but not linked: 49

  1. Bartel, 1990, The recognition component of the N-end rule pathway, EMBO J., 9, 3179, 10.1002/j.1460-2075.1990.tb07516.x · DOI
  2. Crook, 1991, p53 point mutation in HPV negative human cervical carcinoma cell lines, Oncogene, 6, 873
  3. DeCaprio, 1988, SV40 large tumor antigen forms a specific complex with the product of the retinoblastoma susceptibility gene, Cell, 54, 275, 10.1016/0092-8674(88)90559-4 · DOI · Paper page
  4. Diller, 1990, p53 functions as a cell cycle control protein in osteosarcomas, Mol. Cell. Biol., 10, 5772, 10.1128/MCB.10.11.5772 · DOI
  5. Finley, 1991, Ubiquitination, Annu. Rev. Cell Biol., 7, 25, 10.1146/annurev.cb.07.110191.000325 · DOI
  6. Girod, 1993, A major conjugating system in wheat germ extracts involves a 15-kDa ubiquitin-conjugating enzyme (E2) homologous to the yeast UBC4UBC5 gene products, J. Biol. Chem., 268, 955, 10.1016/S0021-9258(18)54026-6 · DOI
  7. Girod, 1993, Homologs of the essential ubiquitin conjugating enzymes UBC1, 4, and 5 in yeast are encoded by a multigene family in Arabidopsis thaliana, Plant J., 3, 10.1046/j.1365-313X.1993.03040545.x · DOI
  8. Glotzer, 1991, Cyclin is degraded by the ubiquitin pathway, Nature, 349, 132, 10.1038/349132a0 · DOI
  9. Goebl, 1988, The yeast cell cycle gene cdc34 encodes a ubiquitin-conjugating enzyme, Science, 241, 1131, 10.1126/science.2842867 · DOI
  10. Goldberg, 1976, Intracellular protein degradation in mammalian and bacterial cells, Annu. Rev. Biochem., 45, 747, 10.1146/annurev.bi.45.070176.003531 · DOI
  11. Gonda, 1989, Universality and structure of the N-end rule, J. Biol. Chem., 264, 16700, 10.1016/S0021-9258(19)84762-2 · DOI
  12. Haas, 1988, The resolution and characterization of putative ubiquitin carrier protein isozymes from rabbit reticulocytes, J. Biol. Chem., 263, 13258, 10.1016/S0021-9258(18)37699-3 · DOI
  13. Hatfield, 1992, Multiple isoforms of ubiquitin-activating enzyme E1 from wheat, J. Biol. Chem., 267, 14799, 10.1016/S0021-9258(18)42110-2 · DOI
  14. Hawley-Nelson, 1989, HPV 16 E6 and E7 proteins cooperate to immortalize human foreskin keratinocytes, EMBO J., 8, 3905, 10.1002/j.1460-2075.1989.tb08570.x · DOI · Paper page
  15. Heller, 1990, A ubiquitin-protein ligase specific for type III protein substrates, J. Biol. Chem., 265, 6532, 10.1016/S0021-9258(19)39177-X · DOI
  16. Hershko, 1992, The ubiquitin system for protein degradation, Annu. Rev. Biochem., 61, 761, 10.1146/annurev.bi.61.070192.003553 · DOI
  17. Hubbert, 1992, Human papillomavirus type 16 E6 increases the degradation rate of p53 in human keratinocytes, J. Virol., 66, 6237, 10.1128/JVI.66.10.6237-6241.1992 · DOI
  18. Huibregtse, 1993, Cloning and expression of the cDNA for E6-AP, a protein that mediates the interaction of the human papillomavirus E6 oncoprotein with p53, Mol. Cell. Biol., 13, 775, 10.1128/MCB.13.2.775 · DOI · Paper page
  19. Huibregtse, 1993, Localization of the E6-AP regions that direct HPV E6 binding, association with p53, and ubiquitination of associated proteins, Mol. Cell. Biol., 13, 4918, 10.1128/MCB.13.8.4918 · DOI · Paper page
  20. Jabben, 1989, Ubiquitin-phytochrome conjugates: pool dynamics during in vivo phytochrome degradation, J. Biol. Chem., 264, 4998, 10.1016/S0021-9258(18)83690-0 · DOI
  21. Jentsch, 1987, The yeast DNA repair gene rad6 encodes a ubiquitin-conjugating enzyme, Nature, 329, 131, 10.1038/329131a0 · DOI
  22. Jentsch, 1991, Genetic analysis of the ubiquitin system, Biochim. Biophys. Acta, 1089, 127, 10.1016/0167-4781(91)90001-3 · DOI
  23. Kaelin, 1992, Expression cloning of a cDNA encoding a retinoblastoma-binding protein with E2F-like properties, Cell, 70, 351, 10.1016/0092-8674(92)90108-O · DOI
  24. Lane, 1979, T antigen is bound to a host protein in SV40-transformed cells, Nature, 278, 261, 10.1038/278261a0 · DOI
  25. Levine, 1991, The p53 tumour suppressor gene, Nature, 351, 453, 10.1038/351453a0 · DOI
  26. Lin, 1990, Transformation by simian virus 40 does not involve the mutational activation of p53 to an oncogenic form, Virology, 176, 302, 10.1016/0042-6822(90)90258-S · DOI
  27. Linzer, 1979, Characterization of a 54K dalton cellular SV40 tumor antigen present in SV40-transformed cells and uninfected embryonal carcinoma cells, Cell, 17, 43, 10.1016/0092-8674(79)90293-9 · DOI
  28. Mietz, 1992, The transcriptional transactivation function of wild-type p53 is inhibited by SV40 large T-antigen and by HPV-16 E6 oncoprotein, EMBO J., 11, 5013, 10.1002/j.1460-2075.1992.tb05608.x · DOI
  29. Münger, 1989, The E6 and E7 genes of the human papillomavirus type 16 together are necessary and sufficient for transformation of primary human keratinocytes, J. Virol., 63, 4417, 10.1128/JVI.63.10.4417-4421.1989 · DOI · Paper page
  30. Oren, 1981, Post-translational regulation of the 54 K cellular tumor antigen in normal and transformed cells, Mol. Cell. Biol., 1, 101, 10.1128/MCB.1.2.101 · DOI
  31. Pickart, 1988, Levels of active ubiquitin carrier proteins decline during erythroid maturation, J. Biol. Chem., 263, 12028, 10.1016/S0021-9258(18)37888-8 · DOI
  32. Quin, 1991, Cloning and characterization of a Saccharomyces cerevisiae gene encoding a new member of the ubiquitin-conjugating protein family, J. Biol. Chem., 266, 15549, 10.1016/S0021-9258(18)98652-7 · DOI
  33. Rechsteiner, 1991, Natural substrates of the ubiquitin proteolytic pathway, Cell, 66, 615, 10.1016/0092-8674(91)90104-7 · DOI
  34. Reich, 1983, Two distinct mechanisms regulate the levels of a cellular tumor antigen, Mol. Cell. Biol., 3, 2143, 10.1128/MCB.3.12.2143 · DOI
  35. Reiss, 1990, Affinity purification of ubiquitin-protein ligase on immobilized protein substrates, J. Biol. Chem., 265, 3685, 10.1016/S0021-9258(19)39648-6 · DOI
  36. Sarnow, 1982, Adenovirus E1b-58kd tumor antigen and SV40 large tumor antigen are physically associated with the same 54 kd cellular protein in transformed cells, Cell, 28, 387, 10.1016/0092-8674(82)90356-7 · DOI
  37. Scheffner, 1990, The E6 oncoprotein encoded by human papillomavirus types 16 and 18 promotes the degradation of p53, Cell, 63, 1129, 10.1016/0092-8674(90)90409-8 · DOI · Paper page
  38. Scheffner, 1992, Targeted degradation of the retinoblastoma protein by human papillomavirus E7-E6 fusion proteins, EMBO J., 11, 2425, 10.1002/j.1460-2075.1992.tb05307.x · DOI
  39. Scheffner, 1992, Interaction of the human papillomavirus type 16 E6 oncoprotein with wild-type and mutant human p53 proteins, J. Virol., 66, 5100, 10.1128/JVI.66.8.5100-5105.1992 · DOI
  40. Seufert, 1990, Ubiquitin conjugating enzymes UBC4 and UBC5 mediate selective degradation of short-lived and abnormal proteins, EMBO J., 9, 543, 10.1002/j.1460-2075.1990.tb08141.x · DOI
  41. Seufert, 1990, UBC1 encodes a novel member of an essential subfamily of yeast ubiquitin-conjugating enzymes involved in protein degradation, EMBO J., 9, 4535, 10.1002/j.1460-2075.1990.tb07905.x · DOI
  42. Sullivan, 1991, Cloning of a 16-kDa ubiquitin carrier protein from wheat and Arabidopsis thaliana, J. Biol. Chem., 266, 23878, 10.1016/S0021-9258(18)54365-9 · DOI
  43. Tobias, 1991, Cloning and functional analysis of the ubiquitin-specific protease gene UBP1 of Saccharomyces cerevisiae, J. Biol. Chem., 266, 12021, 10.1016/S0021-9258(18)99059-9 · DOI
  44. Vierstra, 1993, Protein degradation in plants, Annu. Rev. Plant Physiol. Plant Mol. Biol., 10.1146/annurev.pp.44.060193.002125 · DOI
  45. Werness, 1990, Association of human papillomavirus types 16 and 18 E6 proteins with p53, Science, 248, 76, 10.1126/science.2157286 · DOI · Paper page
  46. Whyte, 1988, Association between an oncogene and an antioncogene: the adenovirus E1A proteins bind to the retinoblastoma gene product, Nature, 334, 124, 10.1038/334124a0 · DOI · Paper page
  47. Wing, 1992, A rabbit reticulocyte ubiquitin carrier protein that supports ubiquitin-dependent proteolysis (E21 4k) is homologous to the yeast DNA repair gene RAD6, J. Biol. Chem., 267, 6495, 10.1016/S0021-9258(19)50455-0 · DOI
  48. Yew, 1992, Inhibition of p53 transactivation required for transformation by adenovirus early 1B protein, Nature, 357, 82, 10.1038/357082a0 · DOI
  49. zur Hausen, 1991, Human papillomaviruses in the pathogenesis of anogenital cancer, Virology, 184, 9, 10.1016/0042-6822(91)90816-T · DOI

Cited by

Metadata

Authors
Scheffner, M., Huibregtse, J. M., Vierstra, R. D., & Howley, P. M.
Venue
Cell
Publisher
Elsevier BV
Published
1993-11
Volume
75
Issue
3
Pages
495-505
ISSN
0092-8674
DOI
10.1016/0092-8674(93)90384-3
Cited by
2,054
References
4
Language
en
Licence
www.elsevier.com/tdm/userlicense/1.0/ (tdm)

About these checks

Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.

Statistics and arithmetic are recomputed, not judged.

Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.

What counts as a claim ›How we measure confidence ›How we check this ›

Are you an author, or do you see a problem with this page? Request a review