caa a22 4500 475846079 CHVBK 20180406123914.0 cr unu---uuuuu 170329e20000401xx s 000 0 eng 10.1007/PL00000728 doi (NATIONALLICENCE)springer-10.1007/PL00000728 Functional analysis of the human MCL-1 gene [Elektronische Daten] [C. Akgul, P. C. Turner, M. R. H. White, S. W. Edwards*] Abstract.: We have isolated a 6.5-kb human genomic fragment that encodes the MCL-1 gene. Comparison of the coding region with the published full-length cDNA reveals that the gene contains three exons and two introns, and that our clone contains 370 bp of the 3′-untranslated region. We have mapped a major transcriptional start site to 80 residues upstream of the translation initiation codon. Reporter gene assays indicate that regulatory sequences responsible for phorbol ester (PMA)-stimulated activity and granulocyte-macrophage-colony-stimulating factor (GM-CSF)-stimulated activity were located within the first 294 bp of the 5′-flanking region upstream from the transcription start site. A deletion mutant was generated that lacked 47 bp between residues −215 and −168: in this mutant, six out of seven GGCCCC repeats and two GCTCA repeats were deleted. Serum-stimulated and GM-CSF-stimulated reporter activity were greatly decreased in this deletion mutant and PMA-stimulated activity was slightly decreased. While the coding and 3′-untranslated regions of the human and mouse genes have significant sequence similarity, there was very little sequence similarity in the 5′-flanking regions of the genes from these two species. Nevertheless, some consensus sequences for a number of transcription-factor-binding sites were detected in the two genes, indicating that transcription may be regulated by similar signalling pathways in these different species. Birkhäuser Verlag Basel,, 2000 Key words. Apoptosis nationallicence Bcl-2 family nationallicence neutrophil nationallicence transcription nationallicence U-937 nationallicence promoter nationallicence luciferase nationallicence Akgul C. School of Biological Sciences, Life Sciences Building, University of Liverpool, Liverpool L69 7ZB (UK), Fax +44 151 794 4349, e-mail: sbir12@liverpool.ac.uk, UK aut Turner P. C. School of Biological Sciences, Life Sciences Building, University of Liverpool, Liverpool L69 7ZB (UK), Fax +44 151 794 4349, e-mail: sbir12@liverpool.ac.uk, UK aut White M. R. H. School of Biological Sciences, Life Sciences Building, University of Liverpool, Liverpool L69 7ZB (UK), Fax +44 151 794 4349, e-mail: sbir12@liverpool.ac.uk, UK aut Edwards* S. W. School of Biological Sciences, Life Sciences Building, University of Liverpool, Liverpool L69 7ZB (UK), Fax +44 151 794 4349, e-mail: sbir12@liverpool.ac.uk, UK aut https://doi.org/10.1007/PL00000728 text/html Onlinezugriff via DOI 1 research-article jats NATIONALLICENCE 856 40 https://doi.org/10.1007/PL00000728 text/html Onlinezugriff via DOI NATIONALLICENCE 700 1- Akgul C. School of Biological Sciences, Life Sciences Building, University of Liverpool, Liverpool L69 7ZB (UK), Fax +44 151 794 4349, e-mail: sbir12@liverpool.ac.uk, UK aut NATIONALLICENCE 700 1- Turner P. C. School of Biological Sciences, Life Sciences Building, University of Liverpool, Liverpool L69 7ZB (UK), Fax +44 151 794 4349, e-mail: sbir12@liverpool.ac.uk, UK aut NATIONALLICENCE 700 1- White M. R. H. School of Biological Sciences, Life Sciences Building, University of Liverpool, Liverpool L69 7ZB (UK), Fax +44 151 794 4349, e-mail: sbir12@liverpool.ac.uk, UK aut NATIONALLICENCE 700 1- Edwards* S. W. School of Biological Sciences, Life Sciences Building, University of Liverpool, Liverpool L69 7ZB (UK), Fax +44 151 794 4349, e-mail: sbir12@liverpool.ac.uk, UK aut Metadata rights reserved Springer special CC-BY-NC licence nationallicence BK010053 XK010053 XK010000 NATIONALLICENCE NATIONALLICENCE NL-springer