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c-Fos/AP-1
AP-1 is not a single protein, but a menagerie of dimeric basic region-leucine zipper (bZIP) proteins that belong to the Jun (c-Jun, JunB, JunD), Fos (c-Fos, FosB, Fra-1 and Fra2), Maf (c-Maf, MafB, MafA, MafG/F/K and Nrl) and ATF (ATF2, LRF1/ATF3, B-ATF, JDP1, JDP2) sub-families, which recognize either 12-O-tetradecanoylphorbol-13-acetate (TPA) response elements (5′-TGAG/CTCA-3′) or cAMP response elements (CRE, 5′-TGACGTCA-3′) Although Jun proteins form very stable heterodimers with Fos- and ATF-family members, they can also homodimerize among themselves. ATF proteins, but not Fos proteins, also form stable homodimers.AP-1 activity is induced by growth factors, cytokines, neurotransmitters, polypeptide hormones, cell–matrix interactions, bacterial and viral infections, and a variety of physical and chemical stresses.
The regulation of AP-1 activity occurs at two major levels: extracellular stimuli modulate both the abundance and the activity of AP-1 proteins.These stimuli activate mitogen activated protein kinase (MAPK) cascades13 that enhance AP-1 activity through the phosphorylation of distinct substrates. The induction of AP-1 by pro-inflammatory cytokines and genotoxic stress is mostly mediated by the JNK and p38 MAPK cascades. Studies examining the function of AP-1 proteins in cell proliferation and oncogenic transformation, based on tissue culture models such as rodent and avian fibroblasts, suggested that c-Jun and the Fos proteins positively regulate cell proliferation, whereas JunB is thought to be a negative regulator.Robust or persistent activation of AP-1 in cells containing damaged DNA causes defective replication and may trigger apoptosis through the same mechanisms that induce cell death after constitutive expression of oncogenes. However, the activation of AP-1 in cells that are able to proliferate promotes cell proliferation and survival.
References
1.Karin M,et al. Curr Opin Cell Biol. 1997 Apr;9(2):240-6.
2.Shaulian E,et al. Nat Cell Biol. 2002 May;4(5):E131-6.
The regulation of AP-1 activity occurs at two major levels: extracellular stimuli modulate both the abundance and the activity of AP-1 proteins.These stimuli activate mitogen activated protein kinase (MAPK) cascades13 that enhance AP-1 activity through the phosphorylation of distinct substrates. The induction of AP-1 by pro-inflammatory cytokines and genotoxic stress is mostly mediated by the JNK and p38 MAPK cascades. Studies examining the function of AP-1 proteins in cell proliferation and oncogenic transformation, based on tissue culture models such as rodent and avian fibroblasts, suggested that c-Jun and the Fos proteins positively regulate cell proliferation, whereas JunB is thought to be a negative regulator.Robust or persistent activation of AP-1 in cells containing damaged DNA causes defective replication and may trigger apoptosis through the same mechanisms that induce cell death after constitutive expression of oncogenes. However, the activation of AP-1 in cells that are able to proliferate promotes cell proliferation and survival.
References
1.Karin M,et al. Curr Opin Cell Biol. 1997 Apr;9(2):240-6.
2.Shaulian E,et al. Nat Cell Biol. 2002 May;4(5):E131-6.