Abstract
mda-7/IL-24 is an unusual member of the IL-10 family of cytokines, with ubiquitous tumor cell pro-apoptotic activity. The mda-7 gene was originally identified on the basis of differential mRNA expression in melanoma cells treated with Interferon β (IFN-β) and protein kinase C activator mezerein (MEZ). MDA-7 protein expression in normal cells is restricted to the immune system and to melanocytes. Based upon its chromosomal localization in an IL-10 family cluster at 1q32, weak amino-acid identity to IL-10 and its 30% amino-acid identity to the other IL-10 family members, mda-7 has now been designated as IL-24. Recent data indicate that this molecule functions as a pro-Th1 cytokine in human PBMCs and as a potent anti-angiogenic molecule. MDA-7 binds and signals through two distinct type II cytokine heterodimeric receptor complexes, IL-20R1/IL-20R2 (IL-20R) and IL-22R1/IL-20R2 (IL-22R), resulting in the activation of STAT3 dependent pathways.
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