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PMID: 8139565 Published · ppublish English Comparative Study Journal Article Research Support, Non-U.S. Gov't

Stimulation of polyomavirus DNA replication by wild-type p53 through the DNA-binding site.

Molecular and cellular biology ·Vol. 14 ·No. 4 ·1994-04-00 ·Pages 2651-63

Kanda T, Segawa K, Ohuchi N, Mori S, Ito Y

Abstract

The tumor suppressor p53 possesses characteristics of a transcription factor; it binds to specific DNA sequences and activates transcription from various promoters. Here we found that murine wild-type p53 stimulated not only transcription but also polyomavirus (Py) DNA replication in a sequence-dependent manner. Oncogenic mutant p53, lacking the DNA-binding activity, showed no stimulation of Py DNA replication. Deletion of the N-terminal acidic transactivation domain of wild-type p53, which completely eliminated the ability to stimulate transcription, only impaired the function to stimulate Py DNA replication. The replication-stimulating activity of wild-type p53 was impaired by the deletion of the C-terminal oligomerization domain as well, without affecting the ability to stimulate transcription. The region responsible for the sequence-specific DNA-binding activity mapped to the central portion of the p53 molecule has a minimal activity. The results indicate that both the N-terminal and the C-terminal regions significantly contribute to the p53-mediated stimulation of Py DNA replication.

Related Genes
p53
MeSH Terms
Amino Acid Sequence Animals Base Sequence Cell Line Chloramphenicol O-Acetyltransferase/biosynthesis,metabolism Conserved Sequence DNA Replication/genetics DNA-Binding Proteins/biosynthesis,metabolism Genes, p53 Kinetics Mice Mice, Inbred BALB C Molecular Sequence Data Oligodeoxyribonucleotides Plasmids Point Mutation Polyomavirus/genetics Promoter Regions, Genetic Restriction Mapping Sequence Deletion Teratoma Transcription, Genetic Transfection Tumor Cells, Cultured Tumor Suppressor Protein p53/biosynthesis,metabolism
Chemicals
DNA-Binding Proteins Oligodeoxyribonucleotides Tumor Suppressor Protein p53 Chloramphenicol O-Acetyltransferase
Authors & Affiliations
5 authors, click to expand affiliations / ORCID
Kanda T
Department of Viral Oncology, Kyoto University, Japan.
Segawa K
Ohuchi N
Mori S
Ito Y
References (63)
63 references, click to expand
  1. Identification of p53 as a sequence-specific DNA-binding protein.
    Science. 1991 Jun 21;252(5013):1708-11 PMID: 2047879
  2. Mutation is required to activate the p53 gene for cooperation with the ras oncogene and transformation.
    J Virol. 1989 Feb;63(2):739-46 PMID: 2642977
  3. 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
  4. p53 alteration is a common event in the spontaneous immortalization of primary BALB/c murine embryo fibroblasts.
    Genes Dev. 1991 Dec;5(12B):2375-85 PMID: 1752433
  5. Regulation of DNA replication in vitro by the transcriptional activation domain of GAL4-VP16.
    Proc Natl Acad Sci U S A. 1992 Jan 15;89(2):589-93 PMID: 1309949
  6. Specific transcription factors stimulate simian virus 40 and polyomavirus origins of DNA replication.
    Mol Cell Biol. 1992 Jun;12(6):2514-24 PMID: 1317005
  7. A transcriptionally active DNA-binding site for human p53 protein complexes.
    Mol Cell Biol. 1992 Jun;12(6):2866-71 PMID: 1588974
  8. Oncogenic forms of p53 inhibit p53-regulated gene expression.
    Science. 1992 May 8;256(5058):827-30 PMID: 1589764
  9. Enhanced binding of a 95 kDa protein to p53 in cells undergoing p53-mediated growth arrest.
    EMBO J. 1992 Jun;11(6):2115-21 PMID: 1600943
  10. Wild-type p53 activates transcription in vitro.
    Nature. 1992 Jul 2;358(6381):83-6 PMID: 1614538
  11. 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
  12. Inhibition of viral and cellular promoters by human wild-type p53.
    J Virol. 1992 Aug;66(8):4757-62 PMID: 1352831
  13. A C-terminal alpha-helix plus basic region motif is the major structural determinant of p53 tetramerization.
    Oncogene. 1992 Aug;7(8):1513-23 PMID: 1321401
  14. Binding of the human E2F transcription factor to the retinoblastoma protein but not to cyclin A is abolished in HPV-16-immortalized cells.
    Oncogene. 1992 Sep;7(9):1681-6 PMID: 1323816
  15. p53 function and dysfunction.
    Cell. 1992 Aug 21;70(4):523-6 PMID: 1505019
  16. Regulation of the specific DNA binding function of p53.
    Cell. 1992 Nov 27;71(5):875-86 PMID: 1423635
  17. 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
  18. Direct interaction between the transcriptional activation domain of human p53 and the TATA box-binding protein.
    J Biol Chem. 1993 Feb 5;268(4):2284-7 PMID: 8428901
  19. Abrogation of p53-mediated transactivation by SV40 large T antigen.
    Oncogene. 1993 Mar;8(3):543-8 PMID: 8382354
  20. Wild-type p53 adopts a 'mutant'-like conformation when bound to DNA.
    EMBO J. 1993 Mar;12(3):1021-8 PMID: 8458320
  21. Definition of a consensus binding site for p53.
    Nat Genet. 1992 Apr;1(1):45-9 PMID: 1301998
  22. Physical and biological features of polyoma virus mutants able to infect embryonal carcinoma cell lines.
    J Virol. 1982 Sep;43(3):800-8 PMID: 6292462
  23. Microinjection of monoclonal antibody to protein p53 inhibits serum-induced DNA synthesis in 3T3 cells.
    Proc Natl Acad Sci U S A. 1982 Oct;79(20):6309-12 PMID: 6292898
  24. Polyoma virus DNA replication requires an enhancer.
    Nature. 1984 Nov 15-21;312(5991):242-6 PMID: 6095089
  25. Monoclonal antibody analysis of p53 expression in normal and transformed cells.
    J Virol. 1986 Aug;59(2):444-52 PMID: 2426467
  26. p53 and DNA polymerase alpha compete for binding to SV40 T antigen.
    Nature. 1987 Oct 1-7;329(6138):456-8 PMID: 3309672
  27. Mouse p53 inhibits SV40 origin-dependent DNA replication.
    Nature. 1987 Oct 1-7;329(6138):458-60 PMID: 2821401
  28. The murine p53 protein blocks replication of SV40 DNA in vitro by inhibiting the initiation functions of SV40 large T antigen.
    Cell. 1989 May 5;57(3):379-92 PMID: 2541911
  29. Transcriptional activator nuclear factor I stimulates the replication of SV40 minichromosomes in vivo and in vitro.
    Cell. 1989 Nov 3;59(3):541-51 PMID: 2553273
  30. Wild-type p53 can inhibit oncogene-mediated focus formation.
    Proc Natl Acad Sci U S A. 1989 Nov;86(22):8763-7 PMID: 2530586
  31. Initiation of eukaryotic DNA replication in vitro.
    Annu Rev Cell Biol. 1989;5:197-245 PMID: 2557059
  32. A tumor promoting phorbol ester, TPA, enhances polyomavirus DNA replication by activating the function of the viral enhancer.
    Oncogene. 1990 Jan;5(1):5-13 PMID: 2157181
  33. Structural aspects of the p53 protein in relation to gene evolution.
    Oncogene. 1990 Jul;5(7):945-52 PMID: 2142762
  34. Presence of a potent transcription activating sequence in the p53 protein.
    Science. 1990 Aug 31;249(4972):1046-9 PMID: 2144363
  35. Transcriptional activation by wild-type but not transforming mutants of the p53 anti-oncogene.
    Science. 1990 Aug 31;249(4972):1049-51 PMID: 2144364
  36. pEF-BOS, a powerful mammalian expression vector.
    Nucleic Acids Res. 1990 Sep 11;18(17):5322 PMID: 1698283
  37. p53 functions as a cell cycle control protein in osteosarcomas.
    Mol Cell Biol. 1990 Nov;10(11):5772-81 PMID: 2233717
  38. Nuclear accumulation of p53 protein is mediated by several nuclear localization signals and plays a role in tumorigenesis.
    Mol Cell Biol. 1990 Dec;10(12):6565-77 PMID: 2247074
  39. Wild-type, but not mutant, human p53 proteins inhibit the replication activities of simian virus 40 large tumor antigen.
    Proc Natl Acad Sci U S A. 1990 Dec;87(23):9275-9 PMID: 2174557
  40. Localization of p53, retinoblastoma and host replication proteins at sites of viral replication in herpes-infected cells.
    Nature. 1991 Jan 31;349(6308):429-31 PMID: 1671528
  41. Mutant p53 proteins bind DNA abnormally in vitro.
    Oncogene. 1991 Jan;6(1):131-6 PMID: 1846954
  42. Cellular localization and cell cycle regulation by a temperature-sensitive p53 protein.
    Genes Dev. 1991 Feb;5(2):151-9 PMID: 1995413
  43. Activation of polyomavirus DNA replication by yeast GAL4 is dependent on its transcriptional activation domains.
    EMBO J. 1991 Apr;10(4):959-69 PMID: 1849079
  44. The nuclear protooncogenes c-jun and c-fos as regulators of DNA replication.
    Proc Natl Acad Sci U S A. 1991 May 1;88(9):3947-51 PMID: 1850842
  45. Cotranslation of activated mutant p53 with wild type drives the wild-type p53 protein into the mutant conformation.
    Cell. 1991 May 31;65(5):765-74 PMID: 2040013
  46. The yeast GAL4 protein transactivates the polyomavirus origin of DNA replication in mouse cells.
    J Virol. 1991 Jul;65(7):3496-503 PMID: 1645781
  47. Wild-type but not mutant p53 immunopurified proteins bind to sequences adjacent to the SV40 origin of replication.
    Cell. 1991 Jun 14;65(6):1083-91 PMID: 1646078
  48. The p53 tumour suppressor gene.
    Nature. 1991 Jun 6;351(6326):453-6 PMID: 2046748
  49. Specific repression of TATA-mediated but not initiator-mediated transcription by wild-type p53.
    Nature. 1993 May 20;363(6426):281-3 PMID: 8387645
  50. The acidic transcriptional activation domains of VP16 and p53 bind the cellular replication protein A and stimulate in vitro BPV-1 DNA replication.
    Cell. 1993 Jun 18;73(6):1207-21 PMID: 8390328
  51. The transactivator proteins VP16 and GAL4 bind replication factor A.
    Cell. 1993 Jun 18;73(6):1223-32 PMID: 8513504
  52. Tight DNA binding and oligomerization are dispensable for the ability of p53 to transactivate target genes and suppress transformation.
    EMBO J. 1993 Jul;12(7):2789-97 PMID: 8334995
  53. Functional domains of wild-type and mutant p53 proteins involved in transcriptional regulation, transdominant inhibition, and transformation suppression.
    Mol Cell Biol. 1993 Sep;13(9):5186-94 PMID: 8355677
  54. Inhibition of DNA replication factor RPA by p53.
    Nature. 1993 Sep 2;365(6441):79-82 PMID: 8361542
  55. Two novel functions associated with the Rel oncoproteins: DNA replication and cell-specific transcriptional activation.
    Oncogene. 1993 Nov;8(11):2889-96 PMID: 8414493
  56. Human p53 binds DNA as a protein homodimer but monomeric variants retain full transcription transactivation activity.
    Oncogene. 1993 Nov;8(11):3165-73 PMID: 8414520
  57. Conformational shifts propagate from the oligomerization domain of p53 to its tetrameric DNA binding domain and restore DNA binding to select p53 mutants.
    EMBO J. 1993 Dec 15;12(13):5057-64 PMID: 8262048
  58. Transformation by polyoma virus middle T-antigen involves the binding and tyrosine phosphorylation of Shc.
    Nature. 1994 Jan 6;367(6458):87-90 PMID: 7509037
  59. High-efficiency transformation of mammalian cells by plasmid DNA.
    Mol Cell Biol. 1987 Aug;7(8):2745-52 PMID: 3670292
  60. Transcriptional elements as components of eukaryotic origins of DNA replication.
    Cell. 1988 Mar 11;52(5):635-8 PMID: 3278812
  61. Activating mutations for transformation by p53 produce a gene product that forms an hsc70-p53 complex with an altered half-life.
    Mol Cell Biol. 1988 Feb;8(2):531-9 PMID: 2832726
  62. Meth A fibrosarcoma cells express two transforming mutant p53 species.
    Oncogene. 1988 Sep;3(3):313-21 PMID: 3060794
  63. p53 mutations in human cancers.
    Science. 1991 Jul 5;253(5015):49-53 PMID: 1905840
Article Info
Journal
Molecular and cellular biology
Abbr.
Mol Cell Biol
ISSN
0270-7306
DOI
10.1128/mcb.14.4.2651-2663.1994
Published
1994-04-00
Pages
2651-63
Language
English
Region
United States
NLM ID
8109087
PMCID
PMC358632
Subset
IM
External Links
PubMed source DOI: 10.1128/mcb.14.4.2651-2663.1994 PMC Full Text View journal details
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