Reciprocal modulatory interaction between human immunodeficiency virus type 1 tat and transcription factor NFAT1

Research output: Contribution to journalArticle

64 Citations (Scopus)

Abstract

Human immunodeficiency virus type 1 (HIV-1) gene expression is regulated by interactions between both viral and host factors. These interactions are also responsible for changes in the expression of many host cell genes, including cytokines and other immune regulators, which may account for the state of immunological dysregulation that characterizes HIV-1 infection. We have investigated the role of a host cell protein, the transcription factor NFAT1, in HIV-1 pathogenesis. We show that NFAT1 interacts with Tat and that this interaction, which involves the major transactivation domain of NFAT1 and the amino-terminal region of Tat, results in a reciprocal modulatory interplay between the proteins: whereas Tat enhances NFAT1-driven transcription in Jurkat T cells, NFAT1 represses Tat-mediated transactivation of the HIV-1 long terminal repeat (LTR). Moreover, NFAT1 binds to the κB sites on the viral LTR and negatively regulates NF-κB-mediated activation of HIV-1 transcription, by competing with NF-κB1 for its binding sites on the HIV-1 LTR. Tat-mediated enhancement of NFAT1 transactivation may explain the upregulation of interleukin 2 and other cytokines that occurs during HIV-1 infection. We discuss the potentially opposing roles of NFAT1 and another family member, NFAT2, in regulating gene transcription of HIV-1 and endogenous cytokine genes.

Original languageEnglish (US)
Pages (from-to)3645-3653
Number of pages9
JournalMolecular and Cellular Biology
Volume19
Issue number5
StatePublished - May 1999
Externally publishedYes

Fingerprint

HIV-1
Transcription Factors
HIV Long Terminal Repeat
Transcriptional Activation
Virus Diseases
Cytokines
tat Gene Products
Genes
Jurkat Cells
Terminal Repeat Sequences
Interleukin-2
Up-Regulation
Binding Sites
T-Lymphocytes
Gene Expression
Proteins

ASJC Scopus subject areas

  • Molecular Biology
  • Genetics
  • Cell Biology

Cite this

Reciprocal modulatory interaction between human immunodeficiency virus type 1 tat and transcription factor NFAT1. / Macian-Juan, Fernando; Rao, Anjana.

In: Molecular and Cellular Biology, Vol. 19, No. 5, 05.1999, p. 3645-3653.

Research output: Contribution to journalArticle

@article{d796a3c03ec94e4dbf8a8aed61550df5,
title = "Reciprocal modulatory interaction between human immunodeficiency virus type 1 tat and transcription factor NFAT1",
abstract = "Human immunodeficiency virus type 1 (HIV-1) gene expression is regulated by interactions between both viral and host factors. These interactions are also responsible for changes in the expression of many host cell genes, including cytokines and other immune regulators, which may account for the state of immunological dysregulation that characterizes HIV-1 infection. We have investigated the role of a host cell protein, the transcription factor NFAT1, in HIV-1 pathogenesis. We show that NFAT1 interacts with Tat and that this interaction, which involves the major transactivation domain of NFAT1 and the amino-terminal region of Tat, results in a reciprocal modulatory interplay between the proteins: whereas Tat enhances NFAT1-driven transcription in Jurkat T cells, NFAT1 represses Tat-mediated transactivation of the HIV-1 long terminal repeat (LTR). Moreover, NFAT1 binds to the κB sites on the viral LTR and negatively regulates NF-κB-mediated activation of HIV-1 transcription, by competing with NF-κB1 for its binding sites on the HIV-1 LTR. Tat-mediated enhancement of NFAT1 transactivation may explain the upregulation of interleukin 2 and other cytokines that occurs during HIV-1 infection. We discuss the potentially opposing roles of NFAT1 and another family member, NFAT2, in regulating gene transcription of HIV-1 and endogenous cytokine genes.",
author = "Fernando Macian-Juan and Anjana Rao",
year = "1999",
month = "5",
language = "English (US)",
volume = "19",
pages = "3645--3653",
journal = "Molecular and Cellular Biology",
issn = "0270-7306",
publisher = "American Society for Microbiology",
number = "5",

}

TY - JOUR

T1 - Reciprocal modulatory interaction between human immunodeficiency virus type 1 tat and transcription factor NFAT1

AU - Macian-Juan, Fernando

AU - Rao, Anjana

PY - 1999/5

Y1 - 1999/5

N2 - Human immunodeficiency virus type 1 (HIV-1) gene expression is regulated by interactions between both viral and host factors. These interactions are also responsible for changes in the expression of many host cell genes, including cytokines and other immune regulators, which may account for the state of immunological dysregulation that characterizes HIV-1 infection. We have investigated the role of a host cell protein, the transcription factor NFAT1, in HIV-1 pathogenesis. We show that NFAT1 interacts with Tat and that this interaction, which involves the major transactivation domain of NFAT1 and the amino-terminal region of Tat, results in a reciprocal modulatory interplay between the proteins: whereas Tat enhances NFAT1-driven transcription in Jurkat T cells, NFAT1 represses Tat-mediated transactivation of the HIV-1 long terminal repeat (LTR). Moreover, NFAT1 binds to the κB sites on the viral LTR and negatively regulates NF-κB-mediated activation of HIV-1 transcription, by competing with NF-κB1 for its binding sites on the HIV-1 LTR. Tat-mediated enhancement of NFAT1 transactivation may explain the upregulation of interleukin 2 and other cytokines that occurs during HIV-1 infection. We discuss the potentially opposing roles of NFAT1 and another family member, NFAT2, in regulating gene transcription of HIV-1 and endogenous cytokine genes.

AB - Human immunodeficiency virus type 1 (HIV-1) gene expression is regulated by interactions between both viral and host factors. These interactions are also responsible for changes in the expression of many host cell genes, including cytokines and other immune regulators, which may account for the state of immunological dysregulation that characterizes HIV-1 infection. We have investigated the role of a host cell protein, the transcription factor NFAT1, in HIV-1 pathogenesis. We show that NFAT1 interacts with Tat and that this interaction, which involves the major transactivation domain of NFAT1 and the amino-terminal region of Tat, results in a reciprocal modulatory interplay between the proteins: whereas Tat enhances NFAT1-driven transcription in Jurkat T cells, NFAT1 represses Tat-mediated transactivation of the HIV-1 long terminal repeat (LTR). Moreover, NFAT1 binds to the κB sites on the viral LTR and negatively regulates NF-κB-mediated activation of HIV-1 transcription, by competing with NF-κB1 for its binding sites on the HIV-1 LTR. Tat-mediated enhancement of NFAT1 transactivation may explain the upregulation of interleukin 2 and other cytokines that occurs during HIV-1 infection. We discuss the potentially opposing roles of NFAT1 and another family member, NFAT2, in regulating gene transcription of HIV-1 and endogenous cytokine genes.

UR - http://www.scopus.com/inward/record.url?scp=0032908409&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0032908409&partnerID=8YFLogxK

M3 - Article

VL - 19

SP - 3645

EP - 3653

JO - Molecular and Cellular Biology

JF - Molecular and Cellular Biology

SN - 0270-7306

IS - 5

ER -