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p53 functional impairment and high p21waf1/cip1 expression in human T-cell lymphotropic/leukemia virus type I-transformed T cells.

Publication ,  Journal Article
Cereseto, A; Diella, F; Mulloy, JC; Cara, A; Michieli, P; Grassmann, R; Franchini, G; Klotman, ME
Published in: Blood
September 1, 1996

Human T-cell lymphotropic/leukemia virus type I (HTLV-I) is associated with T-cell transformation both in vivo and in vitro. Although some of the mechanisms responsible for transformation remain unknown, increasing evidence supports a direct role of viral as well as dysregulated cellular proteins in transformation. We investigated the potential role of the tumor suppressor gene p53 and of the p53-regulated gene, p21waf1/cip1 (wild-type p53 activated fragment 1/cycling dependent kinases [cdks] interacting protein 1), in HTLV-I-infected T cells. We have found that the majority of HTLV-I-infected T cells have the wild-type p53 gene. However, its function in HTLV-I-transformed cells appears to be impaired, as shown by the lack of appropriate p53-mediated responses to ionizing radiation (IR). Interestingly, the expression of the p53 inducible gene, p21waf1/cip1, is elevated at the messenger ribonucleic acid and protein levels in all HTLV-I-infected T-cell lines examined as well as in Taxl-1, a human T-cell line stably expressing Tax. Additionally, Tax induces upregulation of a p21waf1/cip1 promoter-driven luciferase gene in p53 null cells, and increases p21waf1/cip1 expression in Jurkat T cells. These findings suggest that the Tax protein is at least partially responsible for the p53-independent expression of p21waf1/cip1 in HTLV-I-infected cells. Dysregulation of p53 and p21waf1/cip1 proteins regulating cell-cycle progression, may represent an important step in HTLV-I-induced T-cell transformation.

Duke Scholars

Published In

Blood

ISSN

0006-4971

Publication Date

September 1, 1996

Volume

88

Issue

5

Start / End Page

1551 / 1560

Location

United States

Related Subject Headings

  • Tumor Suppressor Protein p53
  • T-Lymphocytes
  • Proteins
  • Protein Biosynthesis
  • Molecular Sequence Data
  • Intracellular Signaling Peptides and Proteins
  • Interleukin-2
  • Immunology
  • Humans
  • Human T-lymphotropic virus 1
 

Citation

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MLA
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Cereseto, A., Diella, F., Mulloy, J. C., Cara, A., Michieli, P., Grassmann, R., … Klotman, M. E. (1996). p53 functional impairment and high p21waf1/cip1 expression in human T-cell lymphotropic/leukemia virus type I-transformed T cells. Blood, 88(5), 1551–1560.
Cereseto, A., F. Diella, J. C. Mulloy, A. Cara, P. Michieli, R. Grassmann, G. Franchini, and M. E. Klotman. “p53 functional impairment and high p21waf1/cip1 expression in human T-cell lymphotropic/leukemia virus type I-transformed T cells.Blood 88, no. 5 (September 1, 1996): 1551–60.
Cereseto A, Diella F, Mulloy JC, Cara A, Michieli P, Grassmann R, et al. p53 functional impairment and high p21waf1/cip1 expression in human T-cell lymphotropic/leukemia virus type I-transformed T cells. Blood. 1996 Sep 1;88(5):1551–60.
Cereseto A, Diella F, Mulloy JC, Cara A, Michieli P, Grassmann R, Franchini G, Klotman ME. p53 functional impairment and high p21waf1/cip1 expression in human T-cell lymphotropic/leukemia virus type I-transformed T cells. Blood. 1996 Sep 1;88(5):1551–1560.

Published In

Blood

ISSN

0006-4971

Publication Date

September 1, 1996

Volume

88

Issue

5

Start / End Page

1551 / 1560

Location

United States

Related Subject Headings

  • Tumor Suppressor Protein p53
  • T-Lymphocytes
  • Proteins
  • Protein Biosynthesis
  • Molecular Sequence Data
  • Intracellular Signaling Peptides and Proteins
  • Interleukin-2
  • Immunology
  • Humans
  • Human T-lymphotropic virus 1