|[Frontiers in Bioscience 2, d49-60, February 15, 1997]|
ROLE OF NF-KappaB IN THE CONTROL OF APOPTOTIC AND PROLIFERATIVE RESPONSES IN IL-2-RESPONSIVE T CELLS|
Javier Gómez, David García-Domingo, Carlos Martínez-A.1 and Angelita Rebollo
Department of Immunology and Oncology, Centro Nacional de Biotecnología, Campus de Cantoblanco, E-28049 Madrid, Spain
Received 1/21/97; Accepted 1/30/97; On-line 2/15/97
IL-2, a 15 kDa glycoprotein, is produced by some T cells; it acts on T cells as a major growth-promoting factor. IL-2 promoter contains an enhancer sequence located between nucleotides -548 to +39 relative to the transcription initiation site. Nuclear factor of activated T cells (NFAT), Oct-1, activating protein-1 (AP1) and NF-kappaB are transcription factors that bind to identified positive elements in the IL-2 promoter. Mutations in the NF-kappaB site of the IL-2 promoter are less deleterious than mutations in the binding sites for other transcription factors. Although most NF-kappaB/Rel family proteins are present in T cells, the heterodimer p50/p65 (NF-kappaB1/Rel A) is the major nuclear factor binding to the NF-kappaB site of the IL-2 promoter (53, 25, 26). In response to extracellular stimuli, p50/p65 is released in T cells from an inactive cytoplasmic pool by rapid phosphorylation and subsequent degradation of the inhibitor IkappaB (33). This release unmasks the nuclear localization signal of NF-kappaB and leads to its translocation to the nucleus (3). Finally, phosphorylation of NF-kappaB may be required for its fully functional activity (48, 49, 25, 26).
c-Rel is also a significant component of the complexes binding to the NF-kappaB site of the IL-2 promoter, and its function may be related to the maintenance rather than to repression of late transcription of IL-2. p50 dimers repress IL-2 gene transcription (49). The function of p52 in IL-2 transcription has not been studied.