Student or educator? Sign up with your school email and get 6 months of Pro free.
CoChat
Sign Up
Cited by 666

The DOI matches its Crossref record; 3 of the 3 references it cites were found in a registry or an index.

Stabilization of the p53 tumor suppressor is induced by adenovirus 5 E1A and accompanies apoptosis.

Open access
Lowe, S W, Ruley, H E·1993·Genes & Development
DOI 10.1101/gad.7.4.535
Open this paper in CoChat — free account

Abstract

Oncogenic transformation by human adenoviruses requires early regions 1A and 1B (E1A and E1B) and provides a model of multistep carcinogenesis. This study shows that the metabolic stabilization of p53 observed in adenovirus 5 (Ad5)-transformed cells can occur in untransformed cells expressing E1A alone. Stabilized p53 was localized to the nucleus and was indistinguishable from wild-type p53 with respect to its interactions with hsc70, PAb420, Ad5 p55E1B, and SV40 large T antigen. Moreover, binding of Ad5 p55E1B or SV40 large T antigen had no additional effect on p53 levels or turnover. Higher levels of p53 were also induced in a variety of cell types within 40 hr after transferring E1A genes. E1A also caused cells to lose viability by a process resembling apoptosis. The apoptosis appeared to involve p53, because p53 levels reverted to normal in surviving cells that had lost E1A, and E1B protected cells from the toxic effects of E1A. These results suggest that (1) the involvement of p53 in tumor suppression and/or apoptosis can be regulated at the level of protein turnover, and (2) a major oncogenic role for E1B is to counter cellular responses to E1A (i.e., stabilization of p53 and associated apoptosis) that preclude transformation by E1A alone. This represents the first physiological setting in which high levels of endogenous p53 are induced in response to an oncogenic challenge, with the apparent consequence of suppressing transformation.

Overview

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

A few free checks a day · papers already verified open instantly · results are public

Integrity signals

Registry

Crossref · 10.1101/gad.7.4.535

Cites

3 of 3 references verified0 citation errors · 0 not checkable

Statistics

Verification

Claims the paper makes

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

A few free checks a day · papers already verified open instantly · results are public

Self-check

Percentages, sums and reported differences re-computed from the paper’s own numbers.

The self-check needs the paper’s full text.

Citations

Cites

Show all 3 references

Research works printed but not linked: 58

  1. 10.1016/0042-6822(87)90441-7 · DOI
  2. 10.1016/0042-6822(86)90272-2 · DOI
  3. 1984, Hygromycin B phosphotransferase as a selectable marker for DNA transfer experiments with higher eucaryotic cells., Mol. Cell. Biol., 4, 2929
  4. 10.1038/329458a0 · DOI
  5. 1986, Evidence for free and metabolically stable p53 protein in nuclear subfractions of simian virus 40-transformed cells., Mol. Cell. Biol., 6, 2233
  6. 1988, Mapping of cellular protein-binding sites on the products of early-region 1A of human adenovirus type 5., Mol. Cell. Biol., 8, 3955
  7. 1988, Meth A fibrosarcoma cells express two transforming mutant p53 species., Oncogene, 3, 313
  8. 10.1073/pnas.86.22.8763 · DOI · Paper page
  9. 10.1016/0092-8674(92)90123-T · DOI
  10. 1988, Activating mutations for transformation by p53 produce a gene product that forms an hsc70-p53 complex with an altered half-life., Mol. Cell. Biol., 8, 531
  11. 1990, Activating mutations in p53 produce a common conformational effect. A monoclonal antibody specific for the mutant form., EMBO J., 9, 1595, 10.1002/j.1460-2075.1990.tb08279.x · DOI
  12. 1984, Energy requirement for degradation of tumor-associated protein p53., Mol. Cell. Biol., 4, 442
  13. 1983, Expression and regulation of Escherichia coli lacZ gene fusions in mammalian cells., J. Mol. Appl. Genet., 2, 101
  14. 1981, Monoclonal antibodies specific for simian virus 40 tumor antigens., J. Virol., 39, 861, 10.1128/jvi.39.3.861-869.1981 · DOI · Paper page
  15. 1985, Monoclonal antibodies specific for adenovirus early region 1A proteins: Extensive heterogeneity in early region 1A products., J. Virol., 55, 533, 10.1128/jvi.55.3.533-546.1985 · DOI · Paper page
  16. 1986, Association of adenovirus early-region 1A proteins with cellular polypeptides., Mol. Cell. Biol., 6, 1579
  17. 1987, Transactivation of host and viral genes by the adenovirus E1B 19K tumor antigen., Oncogene, 2, 25
  18. 1991, Mutant p53 tumor suppressor alleles release ras-induced cell cycle growth arrest., Mol. Cell. Biol., 11, 1344
  19. 1987, Immunological evidence for the association of p53 with a heat shock protein, hsc70, in p53-plus-ras-transformed cell lines., Mol. Cell. Biol., 7, 2863
  20. 1989, Mutation is required to activate the p53 gene for cooperation with the ras oncogene and transformation., J. Virol, 63, 739, 10.1128/jvi.63.2.739-746.1989 · DOI · Paper page
  21. 10.1073/pnas.85.5.1519 · DOI
  22. 1989, Cell lines established by a temperature-sensitive Simian virus 40 large-T-antigen gene are growth restricted at the nonpermissive temperature., Mol. Cell. Biol., 9, 1672
  23. 1987, Activation of adenovirus 5 E1A transcription by region E1B in transformed primary rat cells., EMBO J., 6, 3399, 10.1002/j.1460-2075.1987.tb02663.x · DOI
  24. 1991, Participation of p53 protein in the cellular response to DNA damage., Cancer Res., 51, 6304
  25. 1987, Role of c-myc in the transformation of REF52 cells by viral and cellular oncogenes., Oncogene, 2, 41
  26. 10.1038/278261a0 · DOI
  27. 10.1016/0042-6822(90)90505-L · DOI
  28. 10.1038/351453a0 · DOI
  29. 10.1016/0092-8674(79)90293-9 · DOI
  30. 10.1016/0042-6822(88)90248-6 · DOI
  31. 10.1126/science.1978757 · DOI · Paper page
  32. 1984, UV irradiation stimulates levels of p53 cellular tumor antigen in nontransformed mouse cells., Mol. Cell. Biol., 4, 1689
  33. 1984, Role of the p53 protein in cell proliferation as studied by microinjection of monoclonal antibodies., Mol. Cell. Biol., 4, 276
  34. 1986, Adenovirus-2 E1a and E1b gene products regulate enhancer mediated transcription., Nucleic Acids Res., 14, 9455
  35. 10.1038/320182a0 · DOI
  36. 10.1073/pnas.89.16.7742 · DOI
  37. 10.1038/308199a0 · DOI · Paper page
  38. 1990, Transforming collaborations between ras and nuclear oncogenes., Cancer Cells, 2, 258
  39. 10.1016/0092-8674(82)90356-7 · DOI · Paper page
  40. 10.1016/0092-8674(90)90409-8 · DOI · Paper page
  41. 1986, Morphological transformation of estabished rodent cell lines by high level expression of the adenovirus type 2 E1a gene., Mol. Cell. Biol., 6, 1253
  42. 1990, Nuclear accumulation of p53 protein is mediated by several nuclear localization signals and plays a role in tumorigenesis., Mol. Cell. Biol., 10, 6565
  43. 10.1073/pnas.89.10.4495 · DOI · Paper page
  44. 1987, Inhibition of cell growth mediated by plasmids encoding p53 anti-sense., Oncogene, 1, 277
  45. 10.1038/348747a0 · DOI
  46. 10.1016/0042-6822(83)90264-7 · DOI
  47. 1983, Morphological transformation of human adenoviruses is determined to a large extent by gene products of region E1A., Virology, 131, 362
  48. 1990, Association between the cellular p53 and the adenovirus 5 E1B-55 kd proteins reduces the oncogenicity of Ad-transformed cells., EMBO J., 9, 2621, 10.1002/j.1460-2075.1990.tb07444.x · DOI
  49. 10.1016/0092-8674(89)90913-6 · DOI
  50. 10.1126/science.2157286 · DOI · Paper page
  51. 1990, Role of adenovirus E1B proteins in transformation: Altered organization of intermediate filaments in transformed cells that express the 19-kilodalton protein., Mol. Cell. Biol., 10, 120
  52. 1991, Adenovirus E1B 19-kilodalton protein overcomes the cytoxicity of E1A proteins., J. Virol., 65, 2968, 10.1128/jvi.65.6.2968-2978.1991 · DOI
  53. 1992, The 19-kilodalton adenovirus E1B transforming protein inhibits programmed cell death and prevents cytolysis by tumor necrosis factor α., Mol. Cell. Biol., 12, 2570
  54. 10.1016/0092-8674(89)90984-7 · DOI · Paper page
  55. 10.1038/357082a0 · DOI · Paper page
  56. 10.1038/352345a0 · DOI · Paper page
  57. 10.1101/gad.1.7.645 · DOI
  58. 1985, Adenovirus serotype determines association and localization of the large E1B tumor antigen with cellular tumor antigen p53 in transformed cells., Mol. Cell. Biol., 5, 3084

Cited by

Metadata

Authors
Lowe, S. W., & Ruley, H. E.
Venue
Genes & Development
Publisher
Cold Spring Harbor Laboratory
Published
1993-04
Volume
7
Issue
4
Pages
535-545
ISSN
  • 0890-9369 (ISSN-L)
  • 1549-5477
DOI
10.1101/gad.7.4.535
OpenAlex
W2128366838
Cited by
666
References
3
Type
posted content
Language
en
Open access
diamond

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

Data sources

Bibliographic data: Semantic Scholar, OpenAlex, Crossref.

Contains information from the Semantic Scholar Academic Graph Datasets, made available under the ODC Attribution License (ODC-BY 1.0).

Semantic Scholar’s data is described in: Kinney, R., et al. (2023). The Semantic Scholar Open Data Platform. arXiv:2301.10140.