An essential role for Daxx in the inhibition of B lymphopoiesis by type I interferons.
Interferon-alpha and -beta inhibit the interleukin-7-mediated growth and survival of T and B lymphoid progenitors via an unknown, STAT1-independent pathway. Gene expression profile analysis of interferon-beta-treated progenitor B cells revealed enhanced Daxx expression, with concomitant Daxx protein increase and nuclear body translocation. The interferon effects included downregulation of cell cycle regulating genes and cell cycle arrest, followed by Bcl-2 downregulation and apoptosis. Daxx antisense oligonucleotides rescued the interferon-treated pro-B cells from growth arrest and apoptosis in parallel with the reduction of nuclear Daxx. These findings implicate the gene repressor function of Daxx in interferon-induced apoptosis of lymphoid progenitors.
Gongora
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R
Division of Developmental and Clinical Immunology, Department of Medicine, University of Alabama at Birmingham, Birmingham, AL 35294, USA.
Stephan
R P
RP
Zhang
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Z
Cooper
M D
MD
D016475:3T3 Cells; D048868:Adaptor Proteins, Signal Transducing; D000818:Animals; D017209:Apoptosis / Q000276:immunology; D001402:B-Lymphocytes / Q000166:cytology* / Q000187:drug effects / Q000276:immunology; D002352:Carrier Proteins / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D002453:Cell Cycle; D002478:Cells, Cultured; D056970:Co-Repressor Proteins; D004268:DNA-Binding Proteins / Q000235:genetics / Q000502:physiology; D020869:Gene Expression Profiling; D006412:Hematopoietic Stem Cells / Q000166:cytology* / Q000187:drug effects / Q000276:immunology; D006801:Humans; D016898:Interferon-alpha / Q000276:immunology* / Q000494:pharmacology; D016899:Interferon-beta / Q000276:immunology* / Q000494:pharmacology; D047908:Intracellular Signaling Peptides and Proteins; D019891:Leukopoiesis / Q000276:immunology*; D051379:Mice; D018345:Mice, Knockout; D016513:Mice, SCID; D018832:Molecular Chaperones; D009687:Nuclear Proteins; D050794:STAT1 Transcription Factor; D015534:Trans-Activators / Q000235:genetics / Q000502:physiology; D019014:fas Receptor / Q000096:biosynthesis
D048868:Adaptor Proteins, Signal Transducing; D002352:Carrier Proteins; D056970:Co-Repressor Proteins; C106985:DAXX protein, human; D004268:DNA-Binding Proteins; C491473:Daxx protein, mouse; D016898:Interferon-alpha; D047908:Intracellular Signaling Peptides and Proteins; D018832:Molecular Chaperones; D009687:Nuclear Proteins; D050794:STAT1 Transcription Factor; C494079:STAT1 protein, human; C494080:Stat1 protein, mouse; D015534:Trans-Activators; D019014:fas Receptor; D016899:Interferon-beta