Regulation of expression of the c-sis proto-oncogene

Area of Science:

• Molecular Biology
• Oncogenes
• Gene Regulation

Background:

• Platelet-derived growth factor B (PDGF-B) is encoded by the c-sis proto-oncogene.
• Regulation of PDGF-B expression is crucial in physiological and pathological contexts.
• The 5' untranslated region (UTR) of c-sis mRNA plays a role in gene expression control.

Purpose of the Study:

• To investigate the regulatory elements within the c-sis proto-oncogene.
• To identify sequences in the 5' UTR of c-sis mRNA that affect protein synthesis.
• To analyze the transcriptional regulatory regions upstream of the c-sis RNA initiation site.

Main Methods:

• Deletion analysis of the 5' UTR of c-sis mRNA.
• Identification of sequences important for transcriptional activity.
• Assessment of transcriptional enhancer activity using the human T lymphotropic virus type I (HTLV-I) promoter.
• Investigation of response to HTLV-I transactivator protein.

Main Results:

• Specific sequences within the 1028-nucleotide 5' UTR of c-sis mRNA inhibit protein synthesis.
• Deletion of nucleotides 154-378 or 398-475 relieved this inhibition.
• Sequences between -375 and -99 nucleotides upstream of the RNA CAP site are critical for full transcriptional activity.
• A transcriptional enhancer activity was identified, increasing HTLV-I promoter activity independently of distance and orientation.
• Sequences upstream of the c-sis RNA CAP site responded to the HTLV-I transactivator protein, increasing RNA synthesis.

Conclusions:

• The 5' UTR of c-sis mRNA contains inhibitory elements for protein synthesis.
• Upstream regulatory sequences are essential for full transcriptional activity of the c-sis gene.
• The c-sis gene promoter exhibits enhancer activity and is responsive to viral transactivators, suggesting complex regulatory mechanisms.