FAIM was identified as a protein that was inducibly expressed in B lymphocytes resistant to Fas-mediated apoptosis. Expression of FAIM inhibits receptor-mediated apoptosis in B cells as well as other cell types. FAIM is expressed in germinal center B cells, is positively regulated by IRF-4, and is also capable of inducing IRF-4 expression in a feed-forward mechanism. FAIM also regulates T cell receptor-mediated apoptosis by modulating Akt activation and Nur77 expression. Knockout mice for FAIM show an increased sensitivity to Fas-mediated apoptosis within B and T cells as well as hepatocytes. An alternatively spliced form of FAIM, termed FAIM-L, is found predominantly in the brain. In the nervous system, the originally identified FAIM does not appear to play a role in apoptosis, but rather can promote neurite outgrowth through the activation of Erk and NF-κB pathways. In contrast, FAIM-L does inhibit neuronal cell death triggered by death receptors.
[1] Schneider, T.J. et al. (1999) J Exp Med 189, 949-56.
[2] Huo, J. et al. (2010) J Biol Chem 285, 11827-35.
[3] Segura, M.F. et al. (2007) J Neurosci 27, 11228-41.
[4] Kaku, H. and Rothstein, T.L. (2009) J Immunol 183, 5575-81.
[5] Huo, J. et al. (2009) Cell Death Differ 16, 1062-70.
[6] Zhong, X. et al. (2001) Mol Immunol 38, 65-72.
[7] Sole, C. et al. (2004) J Cell Biol 167, 479-92.
