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Nucleic Acids Research, 1989, Vol. 17, No. 11 4101-4115
© 1989


MOLECULAR BIOLOGY

Regulation of expression of the c-sis proto-oncogene

Lee Ratner*

Departments of Medicine and Molecular Microbiology, Washington University St Louis. MO 63110, USA

*To whom correspondence should be addressed at: Box 8125, 660 S.Euclid, Washington University, St Louis, MO 63110, USA

Received February 23, 1989. Revised April 17, 1989. Accepted April 17, 1989.

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 nucletoides 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.


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