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Journal of Virology, March 2002, p. 2557-2562, Vol. 76, No. 5
0022-538X/02/$04.00+0     DOI: 10.1128/jvi.76.5.2557-2562.2002
Copyright © 2002, American Society for Microbiology. All Rights Reserved.

Mutant Tax Protein from Bovine Leukemia Virus with Enhanced Ability To Activate the Expression of c-fos

*** Shigeru Tajima and Yoko Aida*

Retrovirus Research Unit, RIKEN Tsukuba Institute, Tsukuba, Ibaraki 305-0074, Japan

Received 23 July 2001/ Accepted 16 November 2001

Bovine leukemia virus (BLV) is the etiologic agent of enzootic bovine leukosis. We previously identified several mutants of the BLV Tax protein with an ability to transactivate transcription via the BLV enhancer that is significantly greater than that of the wild-type Tax protein. Moreover, the mutant proteins also activated other viral enhancers, such as the enhancer of human T-cell leukemia virus type 1, which cannot be activated by wild-type BLV Tax. In this study, we demonstrated that the mutant proteins but not wild-type protein activate the upstream sequence of the human c-fos gene, which contains two major cis-acting elements, the CArG box and cyclic AMP-responsive element (CRE) motif. The mutant protein also strongly increased levels of endogenous c-fos mRNA in both human and bovine cell lines. On the other hand, the wild-type Tax protein has no activity to activate the expression of human c-fos, indicating that wild-type BLV Tax might discriminate between human and bovine c-fos promoter sequences. Deletion and point-mutational analysis of the cis-acting elements revealed that both the CArG box and the CRE motif were indispensable for the activation of c-fos by the mutant BLV Tax protein. Our results suggest that the mutant BLV Tax proteins might not only have the ability to enhance the production of virus particles but might also have increased ability to induce leukemia.

* Corresponding author. Mailing address: RIKEN Tsukuba Institute, 3-1-1 Koyadai, Tsukuba, Ibaraki 305-0074, Japan. Phone: 81-298-36-3522. Fax: 81-298-36-9050. E-mail: aida{at}rtc.riken.go.jp.

Journal of Virology, March 2002, p. 2557-2562, Vol. 76, No. 5
0022-538X/02/$04.00+0     DOI: 10.1128/jvi.76.5.2557-2562.2002
Copyright © 2002, American Society for Microbiology. All Rights Reserved.



This article has been cited by other articles:

  • Tajima, S., Tsukamoto, M., Aida, Y. (2003). Latency of Viral Expression In Vivo Is Not Related to CpG Methylation in the U3 Region and Part of the R Region of the Long Terminal Repeat of Bovine Leukemia Virus. J. Virol. 77: 4423-4430 [Abstract] [Full Text]  
  • Tajima, S., Takahashi, M., Takeshima, S.-n., Konnai, S., Yin, S. A., Watarai, S., Tanaka, Y., Onuma, M., Okada, K., Aida, Y. (2003). A Mutant Form of the Tax Protein of Bovine Leukemia Virus (BLV), with Enhanced Transactivation Activity, Increases Expression and Propagation of BLV In Vitro but Not In Vivo. J. Virol. 77: 1894-1903 [Abstract] [Full Text]  


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