The multifunctional eukaryotic protein YB-1 (Y-box binding protein 1) plays a role in DNA reparation, transcription regulation, splicing, and mRNA translation, thereby participating in many crucial events in cells. Its effect is dependent mostly on its amount, and hence, on regulation of its synthesis. Published data on regulation of synthesis of YB-1 mediated by its mRNA 5′ UTR, and specifically on the 5′ UTR length and the presence of TOP-like motifs in this region, are contradictory. Here we report that 5′ UTRs of major forms of human, rabbit, and mouse YB-1 mRNAs are about 140 nucleotides long and contain no TOP-like motifs mentioned in the literature. Also, we have found that YB-1 specifically interacts with the 5′ UTR of its own mRNA within a region of about 100 nucleotides upstream from the start codon. Apart from YB-1, translation of YB-1 mRNA in a cell free system gives an additional product with an extended N-terminus and lower electrophoretic mobility. The start codon for synthesis of the additional product is AUC at position –(60–58) of the same open reading frame as that for the major product. Also, in the cell there is an alternative YB-1 mRNA with exon 1 replaced by a part of intron 1; YB-1 synthesized in vitro from this mRNA contains, instead of its N-terminal A/P domain, 10–11 amino acids encoded by intron 1.
Immunohistochemical method was used to assay for Snail family regulatory proteins of epithelial-mesenchymal transition, their NF-κB coactivator, and the components of VEGF signaling pathway (VEGF and its receptors VEGFR1 and VEGFR2) in 157 specimens of breast tumors. Most tumors did not express SNAI1, while 65% tumors demonstrated mid- or high-level SNAI2 expression. There were significant correlations between the expression of SNAI1, SNAI2, and their NF-κB co-activator. Correlation was also detected between expression of Snail and VEGFR1 protein families in the tumors. In addition, the study revealed tumoral co-expression of SNAI2 and VEGFR2. The data attest to coordinated activation of regulatory proteins of epithelial-mesenchymal transition and the major components of VEGF signaling pathway in breast tumors.
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