| First Author | Lukashev D | Year | 2001 |
| Journal | J Biol Chem | Volume | 276 |
| Issue | 52 | Pages | 48754-63 |
| PubMed ID | 11602577 | Mgi Jnum | J:73517 |
| Mgi Id | MGI:2155591 | Doi | 10.1074/jbc.M104782200 |
| Citation | Lukashev D, et al. (2001) Differential Regulation of Two Alternatively Spliced Isoforms of Hypoxia-inducible Factor-1alpha in Activated T Lymphocytes. J Biol Chem 276(52):48754-63 |
| abstractText | 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-1alpha subunit in antigen receptor-activated T cells. This is explained by a selective up-regulation of alternatively spliced mRNA isoform I.1 that encodes the HIF-1alpha protein without the first 12 N-terminal amino acids. We show that both short (I.1) and long (I.2) HIF-1alpha isoforms display similar DNA binding and transcriptional activities. Major differences were observed between these two HIF-1alpha isoforms in their expression patterns with respect to the resting and activated T lymphocytes in hypoxic and normoxic conditions. The T cell antigen receptor (TCR)-triggered activation of normal ex vivo T cells and differentiated T cells results in up-regulation of expression of I.1 isoform of HIF-1alpha mRNA without an effect on constitutive I.2 HIF-1alpha mRNA expression. The accumulation of I.1 HIF-1alpha mRNA isoform in T lymphocytes is also demonstrated during cytokine-mediated inflammation in vivo, suggesting a physiological role of short HIF-1alpha isoform in activated lymphocytes. The TCR-triggered, protein kinase C and Ca(2+)/calcineurin-mediated HIF-1alpha I.1 mRNA induction is protein synthesis-independent, suggesting that the HIF-1alpha I.1 gene is expressed as an immediate early response gene. Therefore, these data predict a different physiological role of short and long isoforms of HIF-1alpha in resting and activated cells. |
