Abstract
T cell activation involves the sustained accumulation of T cell receptor (TCR) and IL-2 receptor (IL-2R) mediated signaling events that promote cell cycle entry and progression. The Ikaros family of nuclear factors regulate this process by providing thresholds overcome by receptor signaling. T cells with reduced levels of Ikaros activity require fewer TCR engagement events for activation, exhibit a greater proliferative response to IL-2, and are less sensitive to inhibitors of TCR and IL-2R signaling. Upon T cell activation, Ikaros proteins localize in a higher-order chromatin structure where they colocalize with components of the DNA replication machinery. Proliferating T cells with reduced Ikaros activity display chromosome abnormalities. We propose that participation of Ikaros in higher-order chromatin structures controls cell cycle transitions and restricts DNA replication.
Publication types
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Research Support, Non-U.S. Gov't
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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Animals
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Cell Cycle / immunology*
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Cell Cycle Proteins / physiology
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Cell Division / genetics
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Cell Division / immunology
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Cell Nucleus / metabolism
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Chromosome Aberrations / immunology
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Chromosomes / physiology*
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DNA-Binding Proteins*
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Ikaros Transcription Factor
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Interleukin-2 / pharmacology
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Lymphocyte Activation* / genetics
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Mice
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Mice, Inbred C57BL
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Mice, Inbred Strains
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Mutation / immunology
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S Phase / genetics
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S Phase / immunology
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Signal Transduction / genetics
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Signal Transduction / immunology
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T-Lymphocytes / cytology
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T-Lymphocytes / immunology*
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T-Lymphocytes / metabolism
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Transcription Factors / genetics
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Transcription Factors / metabolism
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Transcription Factors / physiology*
Substances
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Cell Cycle Proteins
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DNA-Binding Proteins
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Interleukin-2
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Transcription Factors
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Zfpn1a1 protein, mouse
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Ikaros Transcription Factor