Differential Regulation of Two Alternatively Spliced Isoforms of Hypoxia-inducible Factor-1α in Activated T Lymphocytes
作者： Dmitriy Lukashev , Charles Caldwell , Akio Ohta , Pearl Chen , Michail Sitkovsky
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摘要: Cell adaptation to hypoxia is partially accomplished by hypoxia-inducible transcription factor-1 (HIF-1). Here we report the hypoxia-independent up-regulation of HIF-1α subunit in antigen receptor-activated T cells. This explained a selective alternatively spliced mRNA isoform I.1 that encodes protein without first 12 N-terminal amino acids. We show both short (I.1) and long (I.2) isoforms display similar DNA binding transcriptional activities. Major differences were observed between these two their expression patterns with respect resting activated lymphocytes hypoxic normoxic conditions. The cell receptor (TCR)-triggered activation normal ex vivo cells differentiated results an effect on constitutive I.2 expression. accumulation also demonstrated during cytokine-mediated inflammation vivo, suggesting physiological role lymphocytes. TCR-triggered, kinase C Ca2+/calcineurin-mediated induction synthesis-independent, gene expressed as immediate early response gene. Therefore, data predict different
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