AP-1

Activator Protein-1 (AP-1) is a collective term referring to dimeric transcription factors composed of Jun (v-Jun, c-Jun, JunB, JunD), Fos (v-Fos, c-Fos, FosB, Fra1, Fra2), Jun-dimerization partners (JDP1, JDP2) or ATF (ATF2, ATF3, B-ATF) subunits. They bind to AP-1 DNA recognition elements known as TREs (phorbol 12-O-tetradecanoate-13-acetate response elements) and control cell proliferation, transformation, survival and death.

AP-1 complexes are regulated by controling expression of the subunit genes and by modulating their stability. This is achieved through phosphorylation, mediated by ERK, JNK and p38 MAP kinases. The glucocorticoid receptor is an important inhibitor of AP-1 activity, and other inhibitors include JAB1 and interferon-inducible p202. Differential expression of AP-1 subunit proteins in response to extracellular stimuli, such as growth factors, oncoproteins, cytokines and shortwave length UV irradiation, explains why these transcription factors have such diverse biological actions. For example, pro-mitogenic AP-1 complexes, especially those containing c-Jun, accomplish their growth promoting functions through repression of tumor suppressor genes such as p53, p21^cip1/waf1 and p16. In contrast, JunB-containing AP-1 complexes mediate growth inhibitory and apoptotic functions by upregulating tumor suppressor genes and repressing cyclin D1.

It is very problematic to assign a specific and well-defined biological role to AP-1, as a large array of responses are regulated by this heterogeneous transcription factor. AP-1 contributes to cell growth, proliferation, malignant transformation and, under extreme conditons, activation of the apoptotic cascade.

AP-1 Gene Data