ALTERNATIVE SPLICING ISOFORMS OF REL A GENE IN HUMAN PBMC.

NF-kB has been identified approximately twenty years ago as a nuclear factor that bind the k light chain enhancer in B-cells. The biological system in which NF-kB plays the most important role is the immune system. During these years the role of NF-kB has become apparent in many cellular process, such as cell proliferation and apoptosis regulation. Moreover data show that deregulated activity of NF-kB pathway has been observed and linked to progression of several human diseases including AIDS, stroke, neurodegenerative diseases, diabetes and cancer. NF-kB represents a group of structurally related and evolutionarily conserved proteins, with five members in mammals: p65, p50/p105, p52/p100, c-Rel and RelB. The mammalian NF-kB proteins form homo and heterodimers to bind specific consensus DNA sequences to control gene expression. Proteins of NF-kB family share the same amino acid domain, the Rel Homology Domain (RHD) in which lie sequence for dimerization, binding with inhibitors (IkB), nuclear translocation and DNA binding. Ours previous results indicate the presence of a new mRNA resulting from an alternative splicing from Rel A gene, named p65(-1) mRNA (3) with a shorter RHD. Here we show the expression of p65(-1) mRNA in human PBMC. We have performed RT-PCR on RNA from peripheral blood and p65(-1) appears with two new isoforms. Here we show that these new isoforms are regulated during megakaryocytes differentiation.