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Human T-cell leukemia virus type 1 Tax activates cyclin-dependent kinase inhibitor p21/Waf1/Cip1 expression through a p53-independent mechanism: Inhibition of cdk2.

Publication ,  Journal Article
Chowdhury, IH; Farhadi, A; Wang, X-F; Robb, ML; Birx, DL; Kim, JH
Published in: Int J Cancer
November 20, 2003

We investigated the possible involvement of HTLV-1 Tax in the transcriptional activation of p21/Waf1/Cip1 (hereafter p21), a potent inhibitor of cyclin-dependent kinases and cell growth. Tax transfection resulted in enhanced expression of p21 protein in T and fibroblastoid cells. Similarly, Tax-expressing cells have higher amounts of endogenous p21 protein and RNA. However, neither Tax-negative, HTLV-1 transformed cells or HTLV-1-negative T cell lines had detectable levels of p21 protein and RNA. Cotransfection of Tax strongly activated the p21 promoter. CREB/ATF defective Tax mutant (M47) activated the p21 promoter significantly less efficiently. Tax activated wild type (wt) p21 promoter in p53-negative Jurkat and p53-positive A301cells, irrespective of endogenous p53 status, and activated a mutant p21 promoter containing a p53 responsive element (p53RE) deletion as strongly as wt promoter. Of importance, cdk2 activity was almost completely abolished in Tax-induced p21-expressing MT-2 cells, suggesting that Tax-induced p21 predominantly affects the activity of cdk2, a late G1 and S phase kinase. Taken together, these findings suggest that HTLV-1 Tax activates p21/Waf1/Cip1, a cell growth inhibitor, in a p53-independent mechanism through CREB/ATF-related transcription factors, and inhibits cdk2. Tax induction of p21 may balance the T-cell proliferation function of Tax and may contribute to the long clinical latency of HTLV-1 infection and the delayed development of adult T-cell leukemia.

Duke Scholars

Published In

Int J Cancer

DOI

ISSN

0020-7136

Publication Date

November 20, 2003

Volume

107

Issue

4

Start / End Page

603 / 611

Location

United States

Related Subject Headings

  • Tumor Suppressor Protein p53
  • Tumor Cells, Cultured
  • Transfection
  • Transcriptional Activation
  • Transcription Factors
  • T-Lymphocytes
  • Reverse Transcriptase Polymerase Chain Reaction
  • RNA, Messenger
  • Promoter Regions, Genetic
  • Oncology & Carcinogenesis
 

Citation

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Chowdhury, I. H., Farhadi, A., Wang, X.-F., Robb, M. L., Birx, D. L., & Kim, J. H. (2003). Human T-cell leukemia virus type 1 Tax activates cyclin-dependent kinase inhibitor p21/Waf1/Cip1 expression through a p53-independent mechanism: Inhibition of cdk2. Int J Cancer, 107(4), 603–611. https://doi.org/10.1002/ijc.11316
Chowdhury, Iqbal H., Arash Farhadi, Xiao-Fan Wang, Merlin L. Robb, Deborah L. Birx, and Jerome H. Kim. “Human T-cell leukemia virus type 1 Tax activates cyclin-dependent kinase inhibitor p21/Waf1/Cip1 expression through a p53-independent mechanism: Inhibition of cdk2.Int J Cancer 107, no. 4 (November 20, 2003): 603–11. https://doi.org/10.1002/ijc.11316.
Chowdhury, Iqbal H., et al. “Human T-cell leukemia virus type 1 Tax activates cyclin-dependent kinase inhibitor p21/Waf1/Cip1 expression through a p53-independent mechanism: Inhibition of cdk2.Int J Cancer, vol. 107, no. 4, Nov. 2003, pp. 603–11. Pubmed, doi:10.1002/ijc.11316.
Journal cover image

Published In

Int J Cancer

DOI

ISSN

0020-7136

Publication Date

November 20, 2003

Volume

107

Issue

4

Start / End Page

603 / 611

Location

United States

Related Subject Headings

  • Tumor Suppressor Protein p53
  • Tumor Cells, Cultured
  • Transfection
  • Transcriptional Activation
  • Transcription Factors
  • T-Lymphocytes
  • Reverse Transcriptase Polymerase Chain Reaction
  • RNA, Messenger
  • Promoter Regions, Genetic
  • Oncology & Carcinogenesis