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Journal of Virology, September 2008, p. 8476-8486, Vol. 82, No. 17
0022-538X/08/$08.00+0     doi:10.1128/JVI.00248-08
Copyright © 2008, American Society for Microbiology. All Rights Reserved.

Identification of a Second CtBP Binding Site in Adenovirus Type 5 E1A Conserved Region 3{triangledown}

Rachel K. Bruton,1,{dagger} Peter Pelka,2,{dagger} Katie L. Mapp,1 Gregory J. Fonseca,2 Joseph Torchia,3 Andrew S. Turnell,1 Joe S. Mymryk,2 and Roger J. A. Grand1*

Cancer Research UK Institute for Cancer Studies, University of Birmingham, Birmingham B15 2TT, United Kingdom,1 Departments of Oncology and Microbiology and Immunology, University of Western Ontario, London, Ontario, Canada,2 Departments of Oncology, London Regional Cancer Program, and Biochemistry, University of Western Ontario, London, Ontario, Canada3

Received 4 February 2008/ Accepted 27 May 2008

C-terminal binding protein (CtBP) binds to adenovirus early region 1A (AdE1A) through a highly conserved PXDLS motif close to the C terminus. We now have demonstrated that CtBP1 also interacts directly with the transcriptional activation domain (conserved region 3 [CR3]) of adenovirus type 5 E1A (Ad5E1A) and requires the integrity of the entire CR3 region for optimal binding. The interaction appears to be at least partially mediated through a sequence (161RRNTGDP167) very similar to a recently characterized novel CtBP binding motif in ZNF217 as well as other regions of CR3. Using reporter assays, we further demonstrated that CtBP1 represses Ad5E1A CR3-dependent transcriptional activation. Ad5E1A also appears to be recruited to the E-cadherin promoter through its interaction with CtBP. Significantly, Ad5E1A, CtBP1, and ZNF217 form a stable complex which requires CR3 and the PLDLS motif. It has been shown that Ad513SE1A, containing the CR3 region, is able to overcome the transcriptional repressor activity of a ZNF217 polypeptide fragment in a GAL4 reporter assay through recruitment of CtBP1. These results suggest a hitherto-unsuspected complexity in the association of Ad5E1A with CtBP, with the interaction resulting in transcriptional activation by recruitment of CR3-bound factors to CtBP1-containing complexes.

* Corresponding author. Mailing address: Cancer Research UK, Institute of Cancer Studies, University of Birmingham, Birmingham B15 2TT, United Kingdom. Phone: (44) 121 414 4483. Fax: (44) 121 414 4486. E-mail: r.j.a.grand{at}bham.ac.uk

{triangledown} Published ahead of print on 4 June 2008.

{dagger} These authors contributed equally to this research.

Journal of Virology, September 2008, p. 8476-8486, Vol. 82, No. 17
0022-538X/08/$08.00+0     doi:10.1128/JVI.00248-08
Copyright © 2008, American Society for Microbiology. All Rights Reserved.



This article has been cited by other articles:

  • Pelka, P., Ablack, J. N. G., Torchia, J., Turnell, A. S., Grand, R. J. A., Mymryk, J. S. (2009). Transcriptional control by adenovirus E1A conserved region 3 via p300/CBP. Nucleic Acids Res 37: 1095-1106 [Abstract] [Full Text]  


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