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Functional analysis of the human MCL-1 gene | Cellular and Molecular Life Sciences
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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.
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article, gene, access, privacy, cookies, content, human, genes, data, information, publish, search, life, sciences, transcriptional, activity, transcription, site, analysis, log, journal, research, cmls, mcl, april, akgul, turner, white, region, reporter, regulatory, mutant, open, february, discover, springer, optional, personal, parties, policy, find, track, cellular, molecular, functional, published, cite, edwards, explore, coding,
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granulocyte-macrophage-colony-stimulating factor gm-csf-stimulated reporter activity reporter gene assays transcription-factor-binding sites month download article/chapter related subjects transcriptional circuitry atlas human mcl-1 gene regulatory sequences responsible full article pdf life sciences building privacy choices/manage cookies transcription start site mcl-1 gene april 2000 volume 57 mouse genes european economic area scope submit manuscript translation initiation codon conditions privacy policy similar signalling pathways article cellular functional analysis accepting optional cookies personal data significant sequence similarity liverpool l69 7zb pma-stimulated activity main content log check access instant access 5′-flanking region upstream journal finder publish gene genes data protection gm-csf article log biological sciences article cite life sci article akgul stimulated activity information privacy policy usage analysis access books a optional cookies similar content
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headline:Functional analysis of the human MCL-1 gene
description: 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.
datePublished:
dateModified:
pageStart:684
pageEnd:691
sameAs:https://doi.org/10.1007/PL00000728
keywords:
Key words. Apoptosis; Bcl-2 family; neutrophil; transcription; U-937; promoter; luciferase.
Cell Biology
Biomedicine
general
Life Sciences
Biochemistry
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headline:Functional analysis of the human MCL-1 gene
description: 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.
datePublished:
dateModified:
pageStart:684
pageEnd:691
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Key words. Apoptosis; Bcl-2 family; neutrophil; transcription; U-937; promoter; luciferase.
Cell Biology
Biomedicine
general
Life Sciences
Biochemistry
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