Lymphoid expression and regulation of A20, an inhibitor of programmed cell death.
A20 is a cytokine-inducible primary response gene that encodes a protein that inhibits apoptosis. We cloned and characterized a murine A20 cDNA and mapped the gene to mouse chromosome 10, 3.5 centimorgans proximal to the c-myb locus. Using the murine cDNA, we conducted in situ hybridization studies to examine patterns of A20 expression in mouse embryos and postnatal tissues. Both temporally restricted and tissue-specific patterns of A20 expression were observed, with strikingly high levels in lymphoid organs, including the thymus, spleen, and gut-associated lymphoid tissue. Northern analysis using purified human lymphocyte populations demonstrated that A20 is constitutively expressed in both immature and mature thymocyte subpopulations, as well as in resting peripheral T cells. Activation leads to a down-regulation of A20 expression in both mature thymocytes and peripheral T cells. This pattern of expression and regulation differs markedly from that observed in prior studies with cell lines in which stimulation led to an induction of A20 expression. Additionally, this is the first demonstration of constitutive expression of A20 in primary cells. The data suggest a role for A20 in the function of the lymphoid system.
Graduate Program in Cellular and Molecular Biology, University of Michigan Medical School, Ann Arbor 48109.
M
M
Tewari
F W
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Wolf
M F
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Seldin
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O'Shea
V M
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Dixit
L A
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Turka
D000595:Amino Acid Sequence; D000818:Animals; D017209:Apoptosis; D001483:Base Sequence; D002874:Chromosome Mapping; D003001:Cloning, Molecular; D003433:Crosses, Genetic; D003546:Cysteine Endopeptidases; D004268:DNA-Binding Proteins; D005260:Female; D005786:Gene Expression Regulation; D006801:Humans; D006824:Hybridization, Genetic; D017404:In Situ Hybridization, Fluorescence; D047908:Intracellular Signaling Peptides and Proteins; D008213:Lymphocyte Activation; D008221:Lymphoid Tissue / Q000196:embryology / Q000254:growth & development / Q000378:metabolism*; D008297:Male; D051379:Mice; D008809:Mice, Inbred C3H; D008969:Molecular Sequence Data; D009115:Muridae / Q000235:genetics; D009687:Nuclear Proteins; D014176:Protein Biosynthesis; D011506:Proteins / Q000235:genetics; D016176:T-Lymphocyte Subsets / Q000276:immunology / Q000378:metabolism*; D000072598:Tumor Necrosis Factor alpha-Induced Protein 3; D016335:Zinc Fingers / Q000235:genetics*
D004268:DNA-Binding Proteins; D047908:Intracellular Signaling Peptides and Proteins; D009687:Nuclear Proteins; D011506:Proteins; C076529:TNFAIP3 protein, human; D000072598:Tumor Necrosis Factor alpha-Induced Protein 3; D003546:Cysteine Endopeptidases; C513261:Tnfaip3 protein, mouse