Functional analysis of the human MCL-1 gene


AKGÜL C. , Turner P. C. , White M. R. H. , Edwards S. W.

CELLULAR AND MOLECULAR LIFE SCIENCES, cilt.57, ss.684-691, 2000 (SCI İndekslerine Giren Dergi) identifier identifier identifier identifier

  • Cilt numarası: 57 Konu: 4
  • Basım Tarihi: 2000
  • Doi Numarası: 10.1007/pl00000728
  • Dergi Adı: CELLULAR AND MOLECULAR LIFE SCIENCES
  • Sayfa Sayıları: ss.684-691

Özet

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.