Abstract
The c-myb proto-oncogene product (c-Myb) is a transcriptional activator that can bind to the specific DNA sequences. Although c-Myb also represses an artificial promoter containing the Myb binding sites, natural target genes transcriptionally repressed by c-Myb have not been identified. We have found that the human c-erbB-2 promoter activity is repressed by c-Myb or B-Myb in a chloramphenicol acetyltransferase co-transfection assay. Domain analyses of c-Myb suggested that Myb represses the c-erbB-2 promoter activity by competing with positive regulators of the c-erbB-2 promoter. In in vitro transcription assays, Myb proteins containing only the DNA binding domain could repress c-erbB-2 promoter activity. Two Myb binding sites in the c-erbB-2 promoter were critical for transcriptional repression by c-Myb. One of the two Myb binding sites overlaps the TATA box, and DNase I footprint analyses indicated that c-Myb can compete with TFIID. These results suggest that Myb-induced trans-repression of the c-erbB-2 promoter partly involves competition between Myb and TFIID.
Highlights
All of the gene products of the myb gene family (c, A, and B-Myb) are transcriptional regulators that bind to the specific DNA sequence 5'-AACNG-3' through their DNA binding domains, consisting of three imperfect tandem repeats of 51-52 amino acids 00-14). c-Myb has three functional domains responsible for DNA binding, transcriptional activation, and negative regulation, respectively [5]
Among six Myb binding sites in the c-erbB-2 promoter region, only two sites have sequences that matched with the consensus sequence of the Myb binding sites
The sequences of the four c-Myb binding sites other than sites II and IV are slightly different from this consensus sequence, all of them have the sequence AAC
Summary
Myb gene product; bp, base pairts); Ad MLP, adenovirus major late promoter; CAT, chloramphenicol acetyltransferase. Patients having breast cancers with amplification of the c-erbB-2 gene have a shorter time to relapse as well as a shorter overall survival [34, 35] These findings indicate that control of the c-erbB-2 gene transcription is critical for regulation of cellular proliferation and transformation. It was reported that c-myb expression was inversely correlated with c-erbB-2 overexpression in noninflammatory breast cancer [38] Based on this observation, we have investigated whether c-Myb directly regulates the c-erbB-2 promoter activity. Our results suggest that c-Myb represses the transcription from the c-erbB-2 promoter by directly binding to two sites in the promoter This implies that c-erbB-2 could be a natural target gene repressed by c-Myb
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
