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Journal of Virology, July 2003, p. 7291-7299, Vol. 77, No. 13
0022-538X/03/$08.00+0     DOI: 10.1128/JVI.77.13.7291-7299.2003
Copyright © 2003, American Society for Microbiology. All Rights Reserved.

p21Waf1/Cip1/Sdi1 Prevents Apoptosis as Well as Stimulates Growth in Cells Transformed or Immortalized by Human T-Cell Leukemia Virus Type 1-Encoded Tax

Sanae Kawata, Yasuo Ariumi, and Kunitada Shimotohno*

Institute for Virus Research, Kyoto University, Sakyo-ku, Kyoto 606-8507, Japan

Received 6 December 2002/ Accepted 4 April 2003

Human T-cell leukemia virus type 1 (HTLV-1) Tax regulates the expression of virally encoded genes, as well as various endogenous host genes in trans. Tax-mediated regulation of gene expression is important for the immortalization of normal human T lymphocytes and the transformation of fibroblast cells, such as Rat-1 cells. Tax has the ability to transactivate p21Waf1/Cip1/Sdi1, resulting in high expression levels in HTLV-1-immortalized cells. Since p21 expression is suppressed due to methylation of the promoter region in Rat-l cell line, p21 may not be critical for the transformation of this cell line by Tax. To further understand the role of p21 for the proliferation of Tax-transformed Rat-1 cells, we examined the effect of ectopic expression of p21 in these cells. Here, we observed that p21 expression enhanced the transformation of this cell line via at least two mechanisms: (i) the enhancement of NF-{kappa}B activation and/or CREB signaling and (ii) the excitation of antiapoptotic machinery. To analyze the role of p21 that is overexpressed in HTLV-1-immortalized lymphocytes, p21 expression was suppressed by using an antisense oligonucleotide specific for p21 mRNA; these cells then became sensitive to apoptotic induction. These results suggest that p21 plays an important role in the proliferation of Tax-expressing cells through the regulation of at least two independent mechanisms.

* Corresponding author. Mailing address: Institute for Virus Research, Kyoto University, Sakyo-ku, Kyoto 606-8507, Japan. Phone: 81-75-751-4000. Fax: 81-75-751-3998. E-mail: kshimoto{at}virus.kyoto-u.ac.jp.

Journal of Virology, July 2003, p. 7291-7299, Vol. 77, No. 13
0022-538X/03/$08.00+0     DOI: 10.1128/JVI.77.13.7291-7299.2003
Copyright © 2003, American Society for Microbiology. All Rights Reserved.



This article has been cited by other articles:

  • Sieburg, M., Tripp, A., Ma, J.-W., Feuer, G. (2004). Human T-Cell Leukemia Virus Type 1 (HTLV-1) and HTLV-2 Tax Oncoproteins Modulate Cell Cycle Progression and Apoptosis. J. Virol. 78: 10399-10409 [Abstract] [Full Text]  
  • Jeang, K.-T., Giam, C.-z., Majone, F., Aboud, M. (2004). Life, Death, and Tax: Role of HTLV-I Oncoprotein in Genetic Instability and Cellular Transformation. J. Biol. Chem. 279: 31991-31994 [Full Text]  


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