p53 Functional impairment and high p21(waf1/cip1) expression in human T- cell lymphotropic/leukemia virus type I - Transformed T cells

Anna Cereseto, Francesca Diella, James C. Mulloy, Andrea Cara, Paolo Michieli, Ralph Grassmann, Genoveffa Franchini, Mary E. Klotman

Research output: Contribution to journalArticle

Abstract

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, p21(waf1/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 HTL V- 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, p21(waf1/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 p21(waf1/cip1) promoter- driven luciferase gene in p53 null cells, and increases p21(waf1/cip1) expression in Jurkat T cells. These findings suggest that the Tax protein is at least partially responsible for the p53-independent expression of p21(waf1/cip1) in HTLV-I-infected cells. Dysregulation of p53 and p21(waf1/cip1) proteins regulating cell-cycle progression, may represent an important step in HTLV-I-induced T-cell transformation.

Original languageEnglish
Pages (from-to)1551-1560
Number of pages10
JournalBlood
Volume88
Issue number5
Publication statusPublished - Sep 1 1996

Fingerprint

Human T-lymphotropic virus 1
T-cells
Viruses
T-Lymphocytes
p53 Genes
Genes
tax Gene Products
Cell Line
Null Lymphocytes
Cell Cycle Proteins
Jurkat Cells
Taxation
Ionizing Radiation
Tumor Suppressor Genes
Luciferases
Protein Kinases
Proteins
Up-Regulation
RNA
Ionizing radiation

ASJC Scopus subject areas

  • Hematology

Cite this

Cereseto, A., Diella, F., Mulloy, J. C., Cara, A., Michieli, P., Grassmann, R., ... Klotman, M. E. (1996). p53 Functional impairment and high p21(waf1/cip1) expression in human T- cell lymphotropic/leukemia virus type I - Transformed T cells. Blood, 88(5), 1551-1560.

p53 Functional impairment and high p21(waf1/cip1) expression in human T- cell lymphotropic/leukemia virus type I - Transformed T cells. / Cereseto, Anna; Diella, Francesca; Mulloy, James C.; Cara, Andrea; Michieli, Paolo; Grassmann, Ralph; Franchini, Genoveffa; Klotman, Mary E.

In: Blood, Vol. 88, No. 5, 01.09.1996, p. 1551-1560.

Research output: Contribution to journalArticle

Cereseto, A, Diella, F, Mulloy, JC, Cara, A, Michieli, P, Grassmann, R, Franchini, G & Klotman, ME 1996, 'p53 Functional impairment and high p21(waf1/cip1) expression in human T- cell lymphotropic/leukemia virus type I - Transformed T cells', Blood, vol. 88, no. 5, pp. 1551-1560.
Cereseto, Anna ; Diella, Francesca ; Mulloy, James C. ; Cara, Andrea ; Michieli, Paolo ; Grassmann, Ralph ; Franchini, Genoveffa ; Klotman, Mary E. / p53 Functional impairment and high p21(waf1/cip1) expression in human T- cell lymphotropic/leukemia virus type I - Transformed T cells. In: Blood. 1996 ; Vol. 88, No. 5. pp. 1551-1560.
@article{8e1dd0e177b84bc69ecd60985d7e6f49,
title = "p53 Functional impairment and high p21(waf1/cip1) expression in human T- cell lymphotropic/leukemia virus type I - Transformed T cells",
abstract = "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, p21(waf1/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 HTL V- 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, p21(waf1/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 p21(waf1/cip1) promoter- driven luciferase gene in p53 null cells, and increases p21(waf1/cip1) expression in Jurkat T cells. These findings suggest that the Tax protein is at least partially responsible for the p53-independent expression of p21(waf1/cip1) in HTLV-I-infected cells. Dysregulation of p53 and p21(waf1/cip1) proteins regulating cell-cycle progression, may represent an important step in HTLV-I-induced T-cell transformation.",
author = "Anna Cereseto and Francesca Diella and Mulloy, {James C.} and Andrea Cara and Paolo Michieli and Ralph Grassmann and Genoveffa Franchini and Klotman, {Mary E.}",
year = "1996",
month = "9",
day = "1",
language = "English",
volume = "88",
pages = "1551--1560",
journal = "Blood",
issn = "0006-4971",
publisher = "American Society of Hematology",
number = "5",

}

TY - JOUR

T1 - p53 Functional impairment and high p21(waf1/cip1) expression in human T- cell lymphotropic/leukemia virus type I - Transformed T cells

AU - Cereseto, Anna

AU - Diella, Francesca

AU - Mulloy, James C.

AU - Cara, Andrea

AU - Michieli, Paolo

AU - Grassmann, Ralph

AU - Franchini, Genoveffa

AU - Klotman, Mary E.

PY - 1996/9/1

Y1 - 1996/9/1

N2 - 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, p21(waf1/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 HTL V- 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, p21(waf1/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 p21(waf1/cip1) promoter- driven luciferase gene in p53 null cells, and increases p21(waf1/cip1) expression in Jurkat T cells. These findings suggest that the Tax protein is at least partially responsible for the p53-independent expression of p21(waf1/cip1) in HTLV-I-infected cells. Dysregulation of p53 and p21(waf1/cip1) proteins regulating cell-cycle progression, may represent an important step in HTLV-I-induced T-cell transformation.

AB - 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, p21(waf1/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 HTL V- 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, p21(waf1/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 p21(waf1/cip1) promoter- driven luciferase gene in p53 null cells, and increases p21(waf1/cip1) expression in Jurkat T cells. These findings suggest that the Tax protein is at least partially responsible for the p53-independent expression of p21(waf1/cip1) in HTLV-I-infected cells. Dysregulation of p53 and p21(waf1/cip1) proteins regulating cell-cycle progression, may represent an important step in HTLV-I-induced T-cell transformation.

UR - http://www.scopus.com/inward/record.url?scp=0029817961&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0029817961&partnerID=8YFLogxK

M3 - Article

C2 - 8781409

AN - SCOPUS:0029817961

VL - 88

SP - 1551

EP - 1560

JO - Blood

JF - Blood

SN - 0006-4971

IS - 5

ER -