Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Short Communication
  • Published:

Relationship between E1A binding to cellular proteins, c-myc activation and S-phase induction

Oncogene volume 26, pages 781–787 (2007)Cite this article

Abstract

We recently showed that p300/CREB-binding protein (CBP) plays an important role in maintaining cells in G0/G1 phase by keeping c-myc in a repressed state. Consistent with this, adenovirus E1A oncoprotein induces c-myc in a p300-dependent manner, and the c-myc induction is linked to S-phase induction. The induction of S phase by E1A is dependent on its binding to and inactivating several host proteins including p300/CBP. To determine whether there is a correlation between the host proteins binding to the N-terminal region of E1A, activation of c-myc and induction of S phase, we assayed the c-myc and S-phase induction in quiescent human cells by infecting them with Ad N-terminal E1A mutants with mutations that specifically affect binding to different chromatin-associated proteins including pRb, p300, p400 and p300/CBP-associated factor (PCAF). We show that the mutants that failed to bind to p300 or pRb were severely defective for c-myc and S-phase induction. The induction of c-myc and S phase was only moderately affected when E1A failed to bind to p400. Furthermore, analysis of the E1A mutants that fail to bind to p300, and both p300 and PCAF suggests that PCAF may also play a role in c-myc repression, and that the two chromatin-associated proteins may repress c-myc independently. In summary, these results suggest that c-myc deregulation by E1A through its interaction with these chromatin-associated proteins is an important step in the E1A-mediated cell cycle deregulation and possibly in cell transformation.

This is a preview of subscription content, access via your institution

Access options

Buy this article

  • Purchase on SpringerLink
  • Instant access to the full article PDF.

USD 39.95

Prices may be subject to local taxes which are calculated during checkout

Figure 1
Figure 2
Figure 3
Figure 4

Similar content being viewed by others

References

  • Baluchamy S, Rajabi HN, Thimmapaya R, Navaraj A, Thimmapaya B . (2003). Repression of c-myc and inhibition of G1 exit in cells conditionally overexpressing p300 that is not dependent on its histone acetyltransferase activity. Proc Natl Acad Sci USA 100: 9524–9529.

    Article  CAS  Google Scholar 

  • Barbeau D, Charbonneau R, Whalen SG, Bayley ST, Branton PE . (1994). Functional interactions within adenovirus E1A protein complexes. Oncogene 9: 359–373.

    CAS  PubMed  Google Scholar 

  • Buchmann AM, Swaminathan S, Thimmapaya B . (1998). Regulation of cellular genes in a chromosomal context by the retinoblastoma tumor suppressor protein. Mol Cell Biol 18: 4565–4576.

    Article  CAS  Google Scholar 

  • Chen C, Kang Y, Siegel PM, Massague J . (2002). E2F4/5 and p107 as Smad cofactors linking the TGFbeta receptor to c-myc repression. Cell 110: 19–32.

    Article  CAS  Google Scholar 

  • Doyon Y, Selleck W, Lane WS, Tan S, Cote J . (2004). Structural and functional conservation of the NuA4 histone acetyl transferase complex from yeast to humans. Mol Cell Biol 24: 1884–1896.

    Article  CAS  Google Scholar 

  • Egan C, Jelsma TN, Howe JA, Bayley ST, Ferguson B, Branton PE . (1988). Mapping of cellular protein-binding sites on the products of early-region 1A of human adenovirus type 5. J Virol 8: 3955–3959.

    CAS  Google Scholar 

  • Frisch SM, Mymryk JS . (2002). Adenovirus-5 E1A: paradox and paradigm. Nat Rev Mol Cell Biol 6: 441–4452.

    Article  Google Scholar 

  • Fuchs M, Gerber J, Drapkin R, Sif S, Ikura T, Ogryzko V et al. (2001). The p400 target is an essential E1A transformation target. Cell 106: 297–307.

    Article  CAS  Google Scholar 

  • Goodman RH, Smolik S . (2000). CBP/p300 in cell growth, transformation, and development. Genes Dev 14: 1553–1577.

    CAS  PubMed  Google Scholar 

  • Harbour JW . (2001). Molecular basis of low-penetrance retinoblastoma. Arch Ophthalmol 119: 1699–1704.

    Article  CAS  Google Scholar 

  • Kolli S, Buchmann AM, Williams J, Thimmapaya B . (2001). Antisense-mediated depletion of p300 in human cells leads to premature G1 exit and up-regulation of c-myc. Proc Natl Acad Sci USA 98: 4646–4651.

    Article  CAS  Google Scholar 

  • Lang SE, Hearing P . (2003). The adenovirus E1A oncoprotein recruits the cellular TRRAP/GCN5 histone acetyltransferase complex. Oncogene 22: 2836–2841.

    Article  CAS  Google Scholar 

  • Mitchell KO, El-Deiry WS . (1999). Overexpression of c-myc inhibits p21WAF1/CIP1 expression and induces S-phase entry in 12-O-tetradecanoylphorbol-13-acetate (TPA)-sensitive human cancer cells. Cell Growth Differ 10: 223–230.

    CAS  PubMed  Google Scholar 

  • Moran E . (1993). Interaction of adenoviral proteins with pRB and p53. FASEB J 7: 880–885.

    Article  CAS  Google Scholar 

  • Nees M, Geoghegan JM, Munson P, Prabhu V, Liu Y, Androphy E et al. (2000). Human papillomavirus type 16 E6 and E7 proteins inhibit differentiation-dependent expression of transforming growth factor-beta2 in cervical keratinocytes. Cancer Res 60: 4289–4298.

    CAS  PubMed  Google Scholar 

  • Puri PL, Sartorelli V, Yang X, Hammamor Y, Ogryzko V, Howard B et al. (1997). Differential roles of p300 and PCAF acetyltransferases in muscle differentiation. Mol Cell 1: 35–45.

    Article  CAS  Google Scholar 

  • Rajabi HN, Baluchamy S, Kolli S, Nag A, Srinivas R, Raychaudhari P et al. (2005). Effects of depletion of CREB-binding protein on c-myc regulation and cell cycle G1–S transition. J Biol Chem 280: 361–374.

    Article  CAS  Google Scholar 

  • Reid JL, Bannister AJ, Zegerman P, Martinez-Balbas MA, Kouzarides T . (1998). E1A directly binds and regulates the P/CAF acetyltransferase. EMBO J 17: 4469–4477.

    Article  CAS  Google Scholar 

  • Santoso B, Kadonaga JT . (2006). Reconstitution of chromatin transcription with purified components reveals a chromatin-specific repressive activity of p300. Nat Struct Mol Biol 2: 131–139.

    Article  Google Scholar 

  • Soule HD, Maloney TN, Wolman SR, Peterson WDJ, Brenz R, McGrath C et al. (1990). Isolation and characterization of a spontaneously immortalized human breast epithelial cell line MCF-10. Cancer Res 50: 6075–6086.

    CAS  PubMed  Google Scholar 

  • Sterner DE, Berger SL . (2000). Acetylation of histones and transcription-related factors. Microbiol Mol Biol Rev 64: 435–459.

    Article  CAS  Google Scholar 

  • Taubert S, Gorrini C, Frank SR, Parisi T, Fuchs M, Chan HM et al. (2004). E2F-dependent histone acetylation and recruitment of the Tip60 acetyltransferase complex to chromatin in late G(1). Mol Cell Biol 24: 4546–4556.

    Article  CAS  Google Scholar 

  • Wang H, Moran E, Yaciuk P . (1995). E1A promotes association of p300 and pRB in multimeric complexes required for normal biological activity. J Virol 69: 7917–7924.

    CAS  PubMed  PubMed Central  Google Scholar 

  • Wang HG, Rikitake Y, Carter MC, Yaciuk P, Abraham SE, Zerler B et al. (1993). Identification of specific adenovirus E1A N-terminal residues critical to the binding of cellular proteins and to the control of cell growth. J Virol 67: 476–488.

    CAS  PubMed  PubMed Central  Google Scholar 

Download references

Acknowledgements

This work was supported by the PHS grant CA74403. We are grateful to S Bayely (U McMaster, Canada) for providing certain adenovirus mutants, and W El-Deiry (U Pennsylvania) for providing Adc-myc. We sincerely apologize that because of space limitations, we could not include all the relevant references in this report.

Author information

Author notes

  1. S Baluchamy

    Present address: Department of Genetics and Biochemistry, University of Illinois at Chicago, Chicago, IL, USA

  2. A Navaraj

    Present address: Department of Medicine, University of Pennsylvania School of Medicine, Philadelphia, PA, USA

  3. S Baluchamy and N Sankar: These two authors contributed equally to this work.

Authors and Affiliations

  1. Department of Microbiology–Immunology Feinberg School of Medicine, Northwestern University, Chicago, IL, USA

    S Baluchamy, N Sankar, A Navaraj & B Thimmapaya

  2. Fels Institute for Cancer Research and Molecular Biology, Temple University School of Medicine, Philadelphia, PA, USA

    E Moran

Authors
  1. S Baluchamy
    View author publications

    Search author on:PubMed Google Scholar

  2. N Sankar
    View author publications

    Search author on:PubMed Google Scholar

  3. A Navaraj
    View author publications

    Search author on:PubMed Google Scholar

  4. E Moran
    View author publications

    Search author on:PubMed Google Scholar

  5. B Thimmapaya
    View author publications

    Search author on:PubMed Google Scholar

Corresponding author

Correspondence to B Thimmapaya.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Baluchamy, S., Sankar, N., Navaraj, A. et al. Relationship between E1A binding to cellular proteins, c-myc activation and S-phase induction. Oncogene 26, 781–787 (2007). https://doi.org/10.1038/sj.onc.1209825

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue date:

  • DOI: https://doi.org/10.1038/sj.onc.1209825

Keywords

This article is cited by

Search

Advanced search

Quick links