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PMID: 8643650 Published · ppublish English Comparative Study Journal Article Research Support, Non-U.S. Gov't

E2F1 and E1A(12S) have a homologous activation domain regulated by RB and CBP.

Trouche D, Kouzarides T

Abstract

The E2F1 transcription factor has a well-characterized activation domain at its C terminus and the E1A protein has a recently defined activation domain at its N terminus. Here we show that these activation domains are highly related in sequence. The sequence homology reflects, at least partly, the conservation of common binding sites for the RB and CBP/p300 proteins, which are preserved in the same relative order along E2F1 and E1A. Furthermore, the interaction of RB and CBP with these two activation domains results in the same functional consequences: RB represses both activation domains, whereas CBP stimulates them. We conclude that the activation domains of E1A(12s) and E2F1 belong to a novel functional class, characterized by specific protein binding sites. The implication of this conservation with respect to E1A-induced stimulation of E2F activity is discussed.

MeSH Terms
Adenovirus E1A Proteins/chemistry,metabolism Amino Acid Sequence Binding Sites Bone Neoplasms/pathology CREB-Binding Protein Carrier Proteins Cell Cycle Proteins DNA-Binding Proteins E2F Transcription Factors E2F1 Transcription Factor Humans Molecular Sequence Data Mutagenesis, Site-Directed Nuclear Proteins/metabolism Osteosarcoma/pathology Promoter Regions, Genetic Protein Binding Recombinant Fusion Proteins/biosynthesis Retinoblastoma Protein/metabolism Retinoblastoma-Binding Protein 1 Sequence Homology, Amino Acid Structure-Activity Relationship Trans-Activators Transcription Factor DP1 Transcription Factors/chemistry,metabolism Tumor Cells, Cultured
Chemicals
Adenovirus E1A Proteins Carrier Proteins Cell Cycle Proteins DNA-Binding Proteins E2F Transcription Factors E2F1 Transcription Factor E2F1 protein, human Nuclear Proteins Recombinant Fusion Proteins Retinoblastoma Protein Retinoblastoma-Binding Protein 1 Trans-Activators Transcription Factor DP1 Transcription Factors CREB-Binding Protein CREBBP protein, human
Authors & Affiliations
2 authors, click to expand affiliations / ORCID
Trouche D
Wellcome/Cancer Research Campaign Institute, University of Cambridge, United Kingdom.
Kouzarides T
References (27)
27 references, click to expand
  1. Differential effects of the adenovirus E1A oncogene on members of the AP-1 transcription factor family.
    Mol Cell Biol. 1990 Nov;10(11):5857-64 PMID: 2172787
  2. E1A promotes association between p300 and pRB in multimeric complexes required for normal biological activity.
    J Virol. 1995 Dec;69(12):7917-24 PMID: 7494304
  3. Identification of a conserved region required for hormone dependent transcriptional activation by steroid hormone receptors.
    EMBO J. 1992 Mar;11(3):1025-33 PMID: 1372244
  4. Identification of a growth suppression domain within the retinoblastoma gene product.
    Genes Dev. 1992 Jun;6(6):953-64 PMID: 1534305
  5. Adenovirus E1A makes two distinct contacts with the retinoblastoma protein.
    J Virol. 1992 Jul;66(7):4606-11 PMID: 1534854
  6. A cDNA encoding a pRB-binding protein with properties of the transcription factor E2F.
    Cell. 1992 Jul 24;70(2):337-50 PMID: 1638634
  7. Expression cloning of a cDNA encoding a retinoblastoma-binding protein with E2F-like properties.
    Cell. 1992 Jul 24;70(2):351-64 PMID: 1638635
  8. Conserved motifs in Fos and Jun define a new class of activation domain.
    Genes Dev. 1992 Sep;6(9):1810-9 PMID: 1516835
  9. Promoter-specific trans-activation by the adenovirus E1A12S product involves separate E1A domains.
    Mol Cell Biol. 1992 Oct;12(10):4391-9 PMID: 1406628
  10. Identification of specific adenovirus E1A N-terminal residues critical to the binding of cellular proteins and to the control of cell growth.
    J Virol. 1993 Jan;67(1):476-88 PMID: 8416379
  11. DNA tumor virus transforming proteins and the cell cycle.
    Curr Opin Genet Dev. 1993 Feb;3(1):63-70 PMID: 8453277
  12. E2F-1-mediated transactivation is inhibited by complex formation with the retinoblastoma susceptibility gene product.
    Proc Natl Acad Sci U S A. 1993 Aug 1;90(15):6914-8 PMID: 8346196
  13. Expression of transcription factor E2F1 induces quiescent cells to enter S phase.
    Nature. 1993 Sep 23;365(6444):349-52 PMID: 8377827
  14. Inhibition of E2F-1 transactivation by direct binding of the retinoblastoma protein.
    Mol Cell Biol. 1993 Oct;13(10):6501-8 PMID: 8413249
  15. Identification of distinct roles for separate E1A domains in disruption of E2F complexes.
    Mol Cell Biol. 1993 Nov;13(11):7029-35 PMID: 8413292
  16. The retinoblastoma protein binds E2F residues required for activation in vivo and TBP binding in vitro.
    Nucleic Acids Res. 1993 Nov 11;21(22):4998-5004 PMID: 8255752
  17. Functional interactions within adenovirus E1A protein complexes.
    Oncogene. 1994 Feb;9(2):359-73 PMID: 8290250
  18. Promoter targeting by adenovirus E1a through interaction with different cellular DNA-binding domains.
    Nature. 1994 Apr 7;368(6471):520-5 PMID: 8139685
  19. Nuclear protein CBP is a coactivator for the transcription factor CREB.
    Nature. 1994 Jul 21;370(6486):223-6 PMID: 7913207
  20. Complementary functions of E1a conserved region 1 cooperate with conserved region 3 to activate adenovirus serotype 5 early promoters.
    J Virol. 1994 Aug;68(8):4910-20 PMID: 8035489
  21. An adenovirus E1A transcriptional repressor domain functions as an activator when tethered to a promoter.
    Nucleic Acids Res. 1994 Aug 11;22(15):3053-60 PMID: 8065919
  22. A family of transcriptional adaptor proteins targeted by the E1A oncoprotein.
    Nature. 1995 Mar 2;374(6517):81-4 PMID: 7870178
  23. Adenoviral E1A-associated protein p300 as a functional homologue of the transcriptional co-activator CBP.
    Nature. 1995 Mar 2;374(6517):85-8 PMID: 7870179
  24. DP and E2F proteins: coordinating transcription with cell cycle progression.
    Curr Opin Cell Biol. 1994 Dec;6(6):859-66 PMID: 7880534
  25. p53-mediated apoptosis in HeLa cells can be overcome by excess pRB.
    Oncogene. 1995 Apr 20;10(8):1563-71 PMID: 7731711
  26. Stimulation of E2F1/DP1 transcriptional activity by MDM2 oncoprotein.
    Nature. 1995 Jun 22;375(6533):691-4 PMID: 7791903
  27. Domains of the adenovirus E1A protein required for oncogenic activity are also required for dissociation of E2F transcription factor complexes.
    Genes Dev. 1991 Jul;5(7):1200-11 PMID: 1829698
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
1996-02-20
Pages
1439-42
Language
English
Region
United States
NLM ID
7505876
PMCID
PMC39957
Subset
IM
Grants
Wellcome Trust · United Kingdom
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