Aiolos and Ikaros: regulators of lymphocyte development, homeostasis and lymphoproliferation.
Aiolos and Ikaros encode hemopoietic-specific zinc finger transcription factors that are important regulators of lymphocyte differentiation. Aiolos and Ikaros play a critical role in regulating B and T cell development. Gene targeting studies in mice have shown that inactivation of Ikaros family proteins leads to a complete absence of T, B, NK and dendritic cells, whereas a reduction of Ikaros activity induce hyperproliferation and lymphomas. Aiolos knock-out mice have quantitatively normal lymphoid cells but have chronically activated B cells producing autoantibodies and develop lymphomas with increased frequency. These proteins are involved in the control of gene expression and, associated to nuclear complexes, participate in nucleosome remodeling. This protein family governs cell fate decisions and regulates homeostasis through complex isoforms expression and dimerization. Changes in this regulatory network may reflect differentiation and proliferation adjustments made in lymphoid progenitors and precursors. The direct involvement of aberrant Ikaros protein expression in human hematological oncogenesis, although suggested by several studies, remains to be settled at the genomic level. These points will be discussed in the present review.
Schmitt
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Hôpital Pitié-Salpetrière U543, Bâtiment CERVI, 83, Bd de l'Hôpital F-75651 Paris Cedex 13, France.
Tonnelle
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Dalloul
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Chabannon
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C
Debré
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P
Rebollo
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D000595:Amino Acid Sequence; D000818:Animals; D002454:Cell Differentiation / Q000502:physiology; D004268:DNA-Binding Proteins; D005786:Gene Expression Regulation; D006655:Histone Deacetylases / Q000378:metabolism; D006706:Homeostasis; D006801:Humans; D051740:Ikaros Transcription Factor; D008214:Lymphocytes / Q000502:physiology*; D038041:Lymphopoiesis / Q000502:physiology; D008969:Molecular Sequence Data; D009369:Neoplasms / Q000503:physiopathology; D016415:Sequence Alignment; D015534:Trans-Activators / Q000235:genetics / Q000378:metabolism*; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*; D016335:Zinc Fingers
D004268:DNA-Binding Proteins; C497239:IKZF1 protein, human; C106285:IKZF3 protein, human; D015534:Trans-Activators; D014157:Transcription Factors; D051740:Ikaros Transcription Factor; D006655:Histone Deacetylases