Regulation of expression of the c-sis proto-oncogene

Regulation of expression of platelet derived growth factor polypeptide B encoded by the c-sis proto-oncogene is important in a number of physiological and pathological conditions. Sequences in the 1028 nucleotide long 5' untranslated region of the c-sis mRNA were found to inhibit protein synthesis. The inhibition is relieved by deletion of nucleotides 154-378 or 398-475. Sequences within 375 nucleotides upstream of the RNA initiation site are important for transcriptional activity. Sequences in two portions of this region, between -375 and -235 nucleotides and between -235 and -99 nucleotides relative to the RNA CAP site are important for full activity. A transcriptional enhancer activity is demonstrated by its ability to increase the activity of the human T lymphotropic virus type (HTLV) I promoter at a distance and in an orientation-independent manner. Furthermore, sequences upstream of the c-sis RNA CAP site respond to the HTLV I transactivator protein to increase RNA synthesis from either the c-sis or HTLV I promoter.