Home LiteratureArticle Details
PMID: 8390666 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, P.H.S.

EBNA-5, an Epstein-Barr virus-encoded nuclear antigen, binds to the retinoblastoma and p53 proteins.

Proceedings of the National Academy of Sciences of the United States of America ·Vol. 90 ·No. 12 ·1993-06-15 ·Pages 5455-9

Szekely L, Selivanova G, Magnusson KP, Klein G, Wiman KG

Abstract

Epstein-Barr virus (EBV) immortalized human lymphoblastoid cell lines express six virally encoded nuclear proteins, designated EBV nuclear antigens 1-6 (EBNA-1-6). We show that the EBNA-5 protein (alternatively designated EBNA-LP) that is required for B-cell transformation can form a molecular complex with the retinoblastoma (RB) and p53 tumor suppressor proteins. Using EBNA-5 deletion mutants, we have found that a 66-amino acid-long peptide, encoded by the W repeat of the EBV genome, is sufficient for binding. Point mutations of RB and p53 that inhibit their complexing with other DNA viral oncoproteins do not affect their binding to EBNA-5. p53 competes with RB for EBNA-5 binding. Our data suggest that the mechanisms involved in EBV transformation may include impairment of RB and p53 function.

MeSH Terms
Amino Acid Sequence Antibodies, Monoclonal Antigens, Viral/biosynthesis,metabolism Binding Sites Blotting, Western Burkitt Lymphoma DNA-Binding Proteins/biosynthesis,metabolism Epstein-Barr Virus Nuclear Antigens Glutathione Transferase/metabolism Herpesvirus 4, Human/immunology,metabolism Humans Leukemia, Promyelocytic, Acute Molecular Sequence Data Mutagenesis, Site-Directed Peptides/chemical synthesis Recombinant Fusion Proteins/metabolism Retinoblastoma Protein/metabolism Sequence Deletion Transfection Tumor Cells, Cultured Tumor Suppressor Protein p53/metabolism
Chemicals
Antibodies, Monoclonal Antigens, Viral DNA-Binding Proteins Epstein-Barr Virus Nuclear Antigens Peptides Recombinant Fusion Proteins Retinoblastoma Protein Tumor Suppressor Protein p53 Glutathione Transferase
Authors & Affiliations
5 authors, click to expand affiliations / ORCID
Szekely L
Department of Tumor Biology, Karolinska Institute, Stockholm, Sweden.
Selivanova G
Magnusson K P
Klein G
Wiman K G
References (33)
33 references, click to expand
  1. p53 is frequently mutated in Burkitt's lymphoma cell lines.
    EMBO J. 1991 Oct;10(10):2879-87 PMID: 1915267
  2. Expression of Epstein-Barr virus transformation-associated genes in tissues of patients with EBV lymphoproliferative disease.
    N Engl J Med. 1989 Oct 19;321(16):1080-5 PMID: 2552313
  3. Intranuclear distribution of Epstein-Barr virus-encoded nuclear antigens EBNA-1, -2, -3 and -5.
    J Cell Sci. 1991 Jul;99 ( Pt 3):497-502 PMID: 1658016
  4. The Epstein-Barr virus nuclear protein encoded by the leader of the EBNA RNAs is important in B-lymphocyte transformation.
    J Virol. 1991 Dec;65(12):6826-37 PMID: 1658376
  5. Co-localization of the retinoblastoma protein and the Epstein-Barr virus-encoded nuclear antigen EBNA-5.
    Exp Cell Res. 1991 Dec;197(2):314-8 PMID: 1659990
  6. Point mutations in the abl SH2 domain coordinately impair phosphotyrosine binding in vitro and transforming activity in vivo.
    Mol Cell Biol. 1992 Feb;12(2):609-18 PMID: 1370711
  7. A cDNA encoding a pRB-binding protein with properties of the transcription factor E2F.
    Cell. 1992 Jul 24;70(2):337-50 PMID: 1638634
  8. Expression cloning of a cDNA encoding a retinoblastoma-binding protein with E2F-like properties.
    Cell. 1992 Jul 24;70(2):351-64 PMID: 1638635
  9. A region of the Epstein-Barr virus nuclear antigen leader protein and adenovirus E1A are identical.
    Oncogene. 1988 Dec;3(6):729-30 PMID: 2577878
  10. T antigen is bound to a host protein in SV40-transformed cells.
    Nature. 1979 Mar 15;278(5701):261-3 PMID: 218111
  11. Characterization of a 54K dalton cellular SV40 tumor antigen present in SV40-transformed cells and uninfected embryonal carcinoma cells.
    Cell. 1979 May;17(1):43-52 PMID: 222475
  12. 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
  13. Major deletions in the gene encoding the p53 tumor antigen cause lack of p53 expression in HL-60 cells.
    Proc Natl Acad Sci U S A. 1985 Feb;82(3):790-4 PMID: 2858093
  14. An Epstein-Barr virus transcript from a latently infected, growth-transformed B-cell line encodes a highly repetitive polypeptide.
    Proc Natl Acad Sci U S A. 1986 Dec;83(24):9298-302 PMID: 3025831
  15. Monoclonal and polyclonal antibodies against Epstein-Barr virus nuclear antigen 5 (EBNA-5) detect multiple protein species in Burkitt's lymphoma and lymphoblastoid cell lines.
    J Virol. 1987 Dec;61(12):3870-8 PMID: 2824821
  16. Association between an oncogene and an anti-oncogene: the adenovirus E1A proteins bind to the retinoblastoma gene product.
    Nature. 1988 Jul 14;334(6178):124-9 PMID: 2968522
  17. SV40 large tumor antigen forms a specific complex with the product of the retinoblastoma susceptibility gene.
    Cell. 1988 Jul 15;54(2):275-83 PMID: 2839300
  18. Mapping of cellular protein-binding sites on the products of early-region 1A of human adenovirus type 5.
    Mol Cell Biol. 1988 Sep;8(9):3955-9 PMID: 2975755
  19. The human papilloma virus-16 E7 oncoprotein is able to bind to the retinoblastoma gene product.
    Science. 1989 Feb 17;243(4893):934-7 PMID: 2537532
  20. Mutations in the p53 gene occur in diverse human tumour types.
    Nature. 1989 Dec 7;342(6250):705-8 PMID: 2531845
  21. Association of human papillomavirus types 16 and 18 E6 proteins with p53.
    Science. 1990 Apr 6;248(4951):76-9 PMID: 2157286
  22. The regions of the retinoblastoma protein needed for binding to adenovirus E1A or SV40 large T antigen are common sites for mutations.
    EMBO J. 1990 Apr;9(4):1147-55 PMID: 2138977
  23. A single amino acid substitution results in a retinoblastoma protein defective in phosphorylation and oncoprotein binding.
    Proc Natl Acad Sci U S A. 1990 Sep;87(17):6922-6 PMID: 2168563
  24. The E6 oncoprotein encoded by human papillomavirus types 16 and 18 promotes the degradation of p53.
    Cell. 1990 Dec 21;63(6):1129-36 PMID: 2175676
  25. Identification of cellular proteins that can interact specifically with the T/E1A-binding region of the retinoblastoma gene product.
    Cell. 1991 Feb 8;64(3):521-32 PMID: 1825028
  26. Colony-stimulating factor 1 regulates novel cyclins during the G1 phase of the cell cycle.
    Cell. 1991 May 17;65(4):701-13 PMID: 1827757
  27. The E2F transcription factor is a cellular target for the RB protein.
    Cell. 1991 Jun 14;65(6):1053-61 PMID: 1828392
  28. The T/E1A-binding domain of the retinoblastoma product can interact selectively with a sequence-specific DNA-binding protein.
    Cell. 1991 Jun 14;65(6):1073-82 PMID: 1828394
  29. p53 mutations in human lymphoid malignancies: association with Burkitt lymphoma and chronic lymphocytic leukemia.
    Proc Natl Acad Sci U S A. 1991 Jun 15;88(12):5413-7 PMID: 2052620
  30. Subcellular localization of the retinoblastoma protein.
    Cell Growth Differ. 1991 Jun;2(6):287-95 PMID: 2064997
  31. Cloning of cDNAs for cellular proteins that bind to the retinoblastoma gene product.
    Nature. 1991 Jul 18;352(6332):251-4 PMID: 1857421
  32. Amino-terminal domains of c-myc and N-myc proteins mediate binding to the retinoblastoma gene product.
    Nature. 1991 Aug 8;352(6335):541-4 PMID: 1865909
  33. Mutant p53 detected in a majority of Burkitt lymphoma cell lines by monoclonal antibody PAb240.
    Oncogene. 1991 Sep;6(9):1633-9 PMID: 1923530
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
DOI
10.1073/pnas.90.12.5455
Published
1993-06-15
Pages
5455-9
Language
English
Region
United States
NLM ID
7505876
PMCID
PMC46739
Subset
IM
Grants
NCI NIH HHS · 2 R01 CA14054-19 · United States
External Links
PubMed source DOI: 10.1073/pnas.90.12.5455 PMC Full Text View journal details
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: [email protected]

Copyright © 2026.Genelibs Jinan Honghui Biotechnology Co., Ltd. 鲁ICP备20007159号-2