This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Reprints and Permissions Copyright Information Books from ASM Press MicrobeWorld Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Kawata, S. Articles by Shimotohno, K. Search for Related Content PubMed PubMed Citation Articles by Kawata, S. Articles by Shimotohno, K.

 Previous Article  |  Next Article 

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.

p21^{Waf1/Cip1/Sdi1} Prevents Apoptosis as Well as Stimulates Growth in Cells Transformed or Immortalized by Human T-Cell Leukemia Virus Type 1-Encoded Tax

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 p21^{Waf1/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-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.

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]