ИСТИНА

SLAMF1 (CD150) receptor serves as co-activator molecule expressed on a variety of hematopoietic cells, controlling innate and adaptive immune responses. This receptor is a type I transmembrane glycoprotein of the CD2 family and immunoglobulin (Ig) superfamily. Disorders in regulation of SLAMF1 expression have been identified as important factors for development of autoimmune diseases. Expression of CD150 is low in naive human B cells and becomes upregulated after B cell activation via BCR, CD40, CD180 and signaling after LPS and IL-4 treatment. In our study we investigated the expression of the gene slamf1 (CD150) in human B - lymphoblastoid cell lines. We found that there are two main mRNA isoforms in these cells, one of which contains a number of short upstream open reading frames (uORF) in its 5'- untranslated region (5'UTR) impeding effective translation. It was established that B-cell lines with high expression levels of CD150 protein (MP-1 line) preferably synthesized the short mRNA isoform containing no short uORF, whereas the long mRNA isoform is mainly expressed in the cell line with a relatively low expression level of CD150 (Blin-1 line). The promoter of slamf1 gene was also studied. Using deletion analysis, we showed that the most significant area for CD150 promoter activity is 220 nucleotides upstream of the transcription start point of the short mRNA isoform. This sequence contains binding sites for transcription factors PU.1, IRF4, AP- 1 , Oct2, EBF1, NfkB, SP1. Mutation of EBF1 binding site has reduced promoter activity by 80%; mutations of several other binding sites (PU.1, IRF4, NfkB, SP1 binding sites) also had significant effects on the promoter activity. Additionally, four putative enhancer sequences that can enhance the activity of the putative slamf1 gene promoter were found and functionally tested.