Home LiteratureArticle Details
PMID: 8090749 Published · ppublish English Journal Article Research Support, U.S. Gov't, P.H.S.

Relief of p53-mediated transcriptional repression by the adenovirus E1B 19-kDa protein or the cellular Bcl-2 protein.

Shen Y, Shenk T

Abstract

The p53 tumor suppressor gene product is a transcriptional regulatory protein. It activates transcription from promoters that contain a p53 DNA binding site but represses many promoters that lack its binding site. High-level expression of wild-type p53 can induce apoptosis in certain cell types, and this activity can be blocked by the adenovirus E1B 19-kDa oncoprotein or by the cellular Bcl-2 oncoprotein. Here we report that p53-mediated repression of promoters that lack a p53 binding site is abrogated by the E1B 19-kDa protein or Bcl-2 oncoprotein. In contrast, transcriptional activation by p53 still occurs in the presence of either protein. The fact that two oncoproteins capable of preventing p53-mediated apoptosis also block transcriptional repression by p53 raises the possibility that p53 might induce apoptosis, at least in part, by repressing transcription.

MeSH Terms
Adenovirus E1B Proteins/genetics Apoptosis Cell Nucleus/metabolism Gene Expression Regulation HeLa Cells Humans In Vitro Techniques Promoter Regions, Genetic Proto-Oncogene Proteins/genetics Proto-Oncogene Proteins c-bcl-2 Repressor Proteins/genetics Transcription, Genetic Tumor Suppressor Protein p53/genetics
Chemicals
Adenovirus E1B Proteins Proto-Oncogene Proteins Proto-Oncogene Proteins c-bcl-2 Repressor Proteins Tumor Suppressor Protein p53
Authors & Affiliations
2 authors, click to expand affiliations / ORCID
Shen Y
Howard Hughes Medical Institute, Department of Molecular Biology, Princeton University, NJ 08544-1014.
Shenk T
References (51)
51 references, click to expand
  1. Adenovirus early region 1A enables viral and cellular transforming genes to transform primary cells in culture.
    Nature. 1983 Aug 18-24;304(5927):602-6 PMID: 6308473
  2. Analysis of human p53 proteins and mRNA levels in normal and transformed cells.
    Eur J Biochem. 1986 Feb 3;154(3):665-72 PMID: 2419131
  3. Adenovirus proteins from both E1B reading frames are required for transformation of rodent cells by viral infection and DNA transfection.
    Virology. 1987 Jan;156(1):107-21 PMID: 2949421
  4. The p53 proto-oncogene can act as a suppressor of transformation.
    Cell. 1989 Jun 30;57(7):1083-93 PMID: 2525423
  5. Wild-type p53 can inhibit oncogene-mediated focus formation.
    Proc Natl Acad Sci U S A. 1989 Nov;86(22):8763-7 PMID: 2530586
  6. The adenovirus E1B 19-kilodalton protein stimulates gene expression by increasing DNA levels.
    Mol Cell Biol. 1989 Dec;9(12):5412-23 PMID: 2531284
  7. Role of adenovirus E1B proteins in transformation: altered organization of intermediate filaments in transformed cells that express the 19-kilodalton protein.
    Mol Cell Biol. 1990 Jan;10(1):120-30 PMID: 2136765
  8. Specific disruption of intermediate filaments and the nuclear lamina by the 19-kDa product of the adenovirus E1B oncogene.
    Proc Natl Acad Sci U S A. 1989 Dec;86(24):9886-90 PMID: 2532364
  9. Suppression of human colorectal carcinoma cell growth by wild-type p53.
    Science. 1990 Aug 24;249(4971):912-5 PMID: 2144057
  10. p53 functions as a cell cycle control protein in osteosarcomas.
    Mol Cell Biol. 1990 Nov;10(11):5772-81 PMID: 2233717
  11. Bcl-2 is an inner mitochondrial membrane protein that blocks programmed cell death.
    Nature. 1990 Nov 22;348(6299):334-6 PMID: 2250705
  12. Cellular localization and cell cycle regulation by a temperature-sensitive p53 protein.
    Genes Dev. 1991 Feb;5(2):151-9 PMID: 1995413
  13. Adenovirus E1B 19-kilodalton protein overcomes the cytotoxicity of E1A proteins.
    J Virol. 1991 Jun;65(6):2968-78 PMID: 1851867
  14. Programmed cell death: apoptosis and oncogenesis.
    Cell. 1991 Jun 28;65(7):1097-8 PMID: 1648446
  15. Wild-type p53 induces apoptosis of myeloid leukaemic cells that is inhibited by interleukin-6.
    Nature. 1991 Jul 25;352(6333):345-7 PMID: 1852210
  16. Transcriptional repression by YY1, a human GLI-Krüppel-related protein, and relief of repression by adenovirus E1A protein.
    Cell. 1991 Oct 18;67(2):377-88 PMID: 1655281
  17. Wild-type p53 can down-modulate the activity of various promoters.
    Proc Natl Acad Sci U S A. 1991 Nov 15;88(22):9979-83 PMID: 1946467
  18. Transcriptional and transforming activities of the adenovirus E1A proteins.
    Adv Cancer Res. 1991;57:47-85 PMID: 1835254
  19. Modulation of activity of the promoter of the human MDR1 gene by Ras and p53.
    Science. 1992 Jan 24;255(5043):459-62 PMID: 1346476
  20. Mechanisms and functions of cell death.
    Annu Rev Cell Biol. 1991;7:663-98 PMID: 1809356
  21. Inhibition of p53 transactivation required for transformation by adenovirus early 1B protein.
    Nature. 1992 May 7;357(6373):82-5 PMID: 1533443
  22. Induction of apoptosis by wild-type p53 in a human colon tumor-derived cell line.
    Proc Natl Acad Sci U S A. 1992 May 15;89(10):4495-9 PMID: 1584781
  23. The 19-kilodalton adenovirus E1B transforming protein inhibits programmed cell death and prevents cytolysis by tumor necrosis factor alpha.
    Mol Cell Biol. 1992 Jun;12(6):2570-80 PMID: 1317006
  24. Negative regulation of Rb expression by the p53 gene product.
    Proc Natl Acad Sci U S A. 1992 Jun 15;89(12):5206-10 PMID: 1608930
  25. Wild-type p53 mediates positive regulation of gene expression through a specific DNA sequence element.
    Genes Dev. 1992 Jul;6(7):1143-52 PMID: 1628822
  26. Inhibition of viral and cellular promoters by human wild-type p53.
    J Virol. 1992 Aug;66(8):4757-62 PMID: 1352831
  27. Human wild-type p53 adopts a unique conformational and phosphorylation state in vivo during growth arrest of glioblastoma cells.
    Oncogene. 1992 Aug;7(8):1635-43 PMID: 1630823
  28. Human papillomavirus E6 proteins bind p53 in vivo and abrogate p53-mediated repression of transcription.
    EMBO J. 1992 Aug;11(8):3045-52 PMID: 1379175
  29. The adenovirus E1A proteins induce apoptosis, which is inhibited by the E1B 19-kDa and Bcl-2 proteins.
    Proc Natl Acad Sci U S A. 1992 Aug 15;89(16):7742-6 PMID: 1457005
  30. Repression of the basal c-fos promoter by wild-type p53.
    Nucleic Acids Res. 1992 Aug 11;20(15):4083-7 PMID: 1508692
  31. Modulation of cellular and viral promoters by mutant human p53 proteins found in tumor cells.
    J Virol. 1992 Oct;66(10):6164-70 PMID: 1356162
  32. Growth arrest induced by wild-type p53 protein blocks cells prior to or near the restriction point in late G1 phase.
    Proc Natl Acad Sci U S A. 1992 Oct 1;89(19):9210-4 PMID: 1409626
  33. Defects in a cell cycle checkpoint may be responsible for the genomic instability of cancer cells.
    Cell. 1992 Nov 13;71(4):543-6 PMID: 1423612
  34. Wild-type p53 binds to the TATA-binding protein and represses transcription.
    Proc Natl Acad Sci U S A. 1992 Dec 15;89(24):12028-32 PMID: 1465435
  35. Wild-type mouse p53 down-regulates transcription from different virus enhancer/promoters.
    Oncogene. 1993 Mar;8(3):589-97 PMID: 8382357
  36. Stabilization of the p53 tumor suppressor is induced by adenovirus 5 E1A and accompanies apoptosis.
    Genes Dev. 1993 Apr;7(4):535-45 PMID: 8384579
  37. Wild-type p53 mediates apoptosis by E1A, which is inhibited by E1B.
    Genes Dev. 1993 Apr;7(4):546-54 PMID: 8384580
  38. p53 is required for radiation-induced apoptosis in mouse thymocytes.
    Nature. 1993 Apr 29;362(6423):847-9 PMID: 8479522
  39. Thymocyte apoptosis induced by p53-dependent and independent pathways.
    Nature. 1993 Apr 29;362(6423):849-52 PMID: 8479523
  40. Wild-type but not mutant p53 can repress transcription initiation in vitro by interfering with the binding of basal transcription factors to the TATA motif.
    Oncogene. 1993 May;8(5):1183-93 PMID: 8479742
  41. Specific repression of TATA-mediated but not initiator-mediated transcription by wild-type p53.
    Nature. 1993 May 20;363(6426):281-3 PMID: 8387645
  42. A comparison of the biological activities of wild-type and mutant p53.
    FASEB J. 1993 Jul;7(10):855-65 PMID: 8344485
  43. Bcl-2 heterodimerizes in vivo with a conserved homolog, Bax, that accelerates programmed cell death.
    Cell. 1993 Aug 27;74(4):609-19 PMID: 8358790
  44. p53-dependent apoptosis modulates the cytotoxicity of anticancer agents.
    Cell. 1993 Sep 24;74(6):957-67 PMID: 8402885
  45. The p21 Cdk-interacting protein Cip1 is a potent inhibitor of G1 cyclin-dependent kinases.
    Cell. 1993 Nov 19;75(4):805-16 PMID: 8242751
  46. WAF1, a potential mediator of p53 tumor suppression.
    Cell. 1993 Nov 19;75(4):817-25 PMID: 8242752
  47. Death-defying acts: a meeting review on apoptosis.
    Genes Dev. 1993 Dec;7(12A):2277-84 PMID: 7902825
  48. Adenovirus E1B oncoprotein tethers a transcriptional repression domain to p53.
    Genes Dev. 1994 Jan;8(2):190-202 PMID: 8299938
  49. Immediate early up-regulation of bax expression by p53 but not TGF beta 1: a paradigm for distinct apoptotic pathways.
    Oncogene. 1994 Jun;9(6):1791-8 PMID: 8183578
  50. Tumor suppressor p53 is a regulator of bcl-2 and bax gene expression in vitro and in vivo.
    Oncogene. 1994 Jun;9(6):1799-805 PMID: 8183579
  51. Adenovirus E1b-58kd tumor antigen and SV40 large tumor antigen are physically associated with the same 54 kd cellular protein in transformed cells.
    Cell. 1982 Feb;28(2):387-94 PMID: 6277513
Article Info
Journal
Proceedings of the National Academy of Sciences of the United States of America
Abbr.
Proc Natl Acad Sci U S A
ISSN
0027-8424
Published
1994-09-13
Pages
8940-4
Language
English
Region
United States
NLM ID
7505876
PMCID
PMC44722
Subset
IM
Grants
NCI NIH HHS · CA41086 · United States
Analysis Services
Analysis Services

Contact

No. 2 Wenbo Road, Zhangqiu District, Jinan, Shandong

Qilu Normal University · Genelibs Bioinformatics Lab

750 Shunhua Rd, Jinan

2F, Bldg F, University Science Park

Tel: 0531-88819269

WeChat Official Account

Follow our WeChat subscription account for real-time updates and the latest in medical and biological research.


Business Email

E-mail: product@genelibs.com