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Journal of Virology, October 2008, p. 9381-9388, Vol. 82, No. 19
0022-538X/08/$08.00+0     doi:10.1128/JVI.00791-08
Copyright © 2008, American Society for Microbiology. All Rights Reserved.

Adenovirus E4orf4 Protein Downregulates MYC Expression through Interaction with the PP2A-B55 Subunit{triangledown}

Haggit Ben-Israel,1,{dagger} Rakefet Sharf,1,{dagger} Gideon Rechavi,2 and Tamar Kleinberger1*

The Gonda Center of Molecular Microbiology and The Rappaport Family Institute for Research in the Medical Sciences, Faculty of Medicine, Technion—Israel Institute of Technology, Bat Galim, Haifa 31096,1 Cancer Research Center, Chaim Sheba Medical Center, Tel-Hashomer and Sackler School of Medicine, Tel-Aviv University, Tel-Aviv, Israel2

Received 14 April 2008/ Accepted 11 July 2008

The adenovirus E4 open reading frame 4 (E4orf4) protein is a multifunctional viral regulator that is involved in the temporal regulation of viral gene expression by modulating cellular and viral genes at the transcription and translation levels and by controlling alternative splicing of adenoviral late mRNAs. When expressed individually, E4orf4 induces apoptosis in transformed cells. Using oligonucleotide microarray analysis, validated by quantitative real time PCR, we found that MYC (also known as c-Myc) is downregulated early after the induction of E4orf4 expression. As a result, Myc protein levels are reduced in E4orf4-expressing cells. MYC downregulation is observed both when E4orf4 is expressed individually and within the context of viral infection. E4orf4 reduces MYC transcription but does not affect transcriptional elongation or RNA stability. An interaction with the PP2A-B55 subunit is required for the downregulation of MYC by E4orf4. Since Myc overexpression was previously shown to inhibit adenovirus replication, the downregulation of Myc by E4orf4 would contribute to efficient virus infection.

* Corresponding author. Mailing address: The Gonda Center of Molecular Microbiology, Faculty of Medicine, Technion—Israel Institute of Technology, Bat Galim, Haifa 31096, Israel. Phone: 972-4-8295257. Fax: 972-4-8295225. E-mail: tamark{at}tx.technion.ac.il

{triangledown} Published ahead of print on 23 July 2008.

{dagger} H.B.-I. and R.S. contributed equally to the work.

Journal of Virology, October 2008, p. 9381-9388, Vol. 82, No. 19
0022-538X/08/$08.00+0     doi:10.1128/JVI.00791-08
Copyright © 2008, American Society for Microbiology. All Rights Reserved.



This article has been cited by other articles:

  • Li, S., Brignole, C., Marcellus, R., Thirlwell, S., Binda, O., McQuoid, M. J., Ashby, D., Chan, H., Zhang, Z., Miron, M.-J., Pallas, D. C., Branton, P. E. (2009). The Adenovirus E4orf4 Protein Induces G2/M Arrest and Cell Death by Blocking Protein Phosphatase 2A Activity Regulated by the B55 Subunit. J. Virol. 83: 8340-8352 [Abstract] [Full Text]  


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