IRF-4 activities in HTLV-I-induced T cell leukemogenesis.

Abstract

We summarize recent studies on the activation and regulation of interferon (IFN) regulatory factor-4 (IRF-4) and its function in activated T cells, human T cell lymphoma virus (HTLV-I)-infected T cells, and HTLV-I-induced adult T cell leukemia (ATL). We have examined the specific mechanisms underlying the expression and regulation of the IRF-4 transcription factor in HTLV-I-infected cells and have shown that constitutive IRF-4 expression is exclusive to the transformed, leukemic ATL phenotype as opposed to the nonleukemic HTLV-I associated myelopathies/tropical spastic paraparesis (HAM/TSP) phenotype. In contrast, IRF-4 is only transiently induced in T lymphocytes activated by signals that mimic stimulation through the T cell receptor (TCR). In vivo and in vitro analyses have identified several regulatory regions within the human IRF-4 promoter that interact with the transcriptional regulators NF-kappaB, NF-AT, and Sp-1 to drive IRF-4 production in HTLV-I-infected, ATL-derived cells. cDNA array analysis of an IRF-4-expressing T cell line has also provided valuable insight into potential IRF-4 target genes. Further investigation of these novel IRF-4-regulated genes will permit a mechanistic understanding of IRF-4 function in HTLV-I-induced leukemogenesis.

• Authors: Yael Mamane, Sonia Sharma, Nathalie Grandvaux, Eduardo Hernandez, John Hiscott
• Journal: Journal of interferon & cytokine research : the official journal of the International Society for Interferon and Cytokine Research (J Interferon Cytokine Res) Vol. 22 Issue 1 Pg. 135-43 (Jan 2002) ISSN: 1079-9907 [Print] United States
• PMID: 11846984 (Publication Type: Journal Article, Review)

Chemical References

• DNA-Binding Proteins
• HSP90 Heat-Shock Proteins
• Interferon Regulatory Factors
• Receptors, Antigen, T-Cell
• Transcription Factors
• interferon regulatory factor-4
• Tacrolimus Binding Proteins
• tacrolimus binding protein 4

Topics

• Animals
• DNA-Binding Proteins (metabolism)
• Gene Expression Regulation, Leukemic
• HSP90 Heat-Shock Proteins (metabolism)
• Human T-lymphotropic virus 1 (pathogenicity)
• Humans
• Interferon Regulatory Factors
• Leukemia-Lymphoma, Adult T-Cell (genetics, metabolism, virology)
• Promoter Regions, Genetic
• Protein Processing, Post-Translational
• Receptors, Antigen, T-Cell (metabolism)
• Signal Transduction
• T-Lymphocytes (metabolism, virology)
• Tacrolimus Binding Proteins (metabolism)
• Transcription Factors (metabolism)
• Transcriptional Activation