IRF-4 activities in HTLV-I-induced T cell leukemogenesis.
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.
Mamane
Yael
Y
Terry Fox Molecular Oncology Group, Lady Davis Institute for Medical Research, and Department of Microbiology & Immunology, McGill University, Montreal, Canada.
Sharma
Sonia
S
Grandvaux
Nathalie
N
Hernandez
Eduardo
E
Hiscott
John
J
D000818:Animals; D004268:DNA-Binding Proteins / Q000378:metabolism*; D015973:Gene Expression Regulation, Leukemic; D018841:HSP90 Heat-Shock Proteins / Q000378:metabolism; D015368:Human T-lymphotropic virus 1 / Q000472:pathogenicity*; D006801:Humans; D050835:Interferon Regulatory Factors; D015459:Leukemia-Lymphoma, Adult T-Cell / Q000235:genetics / Q000378:metabolism* / Q000821:virology; D011401:Promoter Regions, Genetic; D011499:Protein Processing, Post-Translational; D011948:Receptors, Antigen, T-Cell / Q000378:metabolism; D015398:Signal Transduction; D013601:T-Lymphocytes / Q000378:metabolism / Q000821:virology; D022021:Tacrolimus Binding Proteins / Q000378:metabolism; D014157:Transcription Factors / Q000378:metabolism*; D015533:Transcriptional Activation; D000099218:Interferon Regulatory Factor-4
D004268:DNA-Binding Proteins; D018841:HSP90 Heat-Shock Proteins; D050835:Interferon Regulatory Factors; D011948:Receptors, Antigen, T-Cell; D022021:Tacrolimus Binding Proteins; D014157:Transcription Factors; D000099218:Interferon Regulatory Factor-4; C403485:tacrolimus binding protein 4