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Two conserved regio...
Two conserved regions within the tissue-type plasminogen activator gene promoter mediate regulation by brain-derived neurotrophic factor
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Daniel, Philip B (author)
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Lux, Wolfram (author)
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Samson, Andre L (author)
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Schleuning, Wolf-Dieter (author)
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Niego, Be'eri (author)
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Weiss, Thomas W. (author)
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- Tjärnlund-Wolf, Anna, 1974 (author)
- Gothenburg University,Göteborgs universitet,Institutionen för neurovetenskap och fysiologi, sektionen för klinisk neurovetenskap och rehabilitering,Institute of Neuroscience and Physiology, Department of Clinical Neuroscience and Rehabilitation
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Medcalf, Robert L. (author)
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(creator_code:org_t)
- 2007-04-05
- 2007
- English.
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In: The FEBS Journal. - : Wiley. - 1742-464X. ; 274:Issue 9, s. 2411-23
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Abstract
Subject headings
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- Tissue-type plasminogen activator (t-PA) has recently been identified as a modulator of neuronal plasticity and can initiate conversion of the pro-form of brain-derived neurotrophic factor (BDNF) into its mature form. BDNF also increases t-PA gene expression implicating t-PA as a downstream effector of BDNF function. Here we demonstrate that BDNF-mediated induction of t-PA mRNA requires an increase in t-PA gene transcription. Reporter constructs harboring 9.5 kb of the human t-PA promoter conferred BDNF-responsiveness in transfected mouse primary cortical neurons. This regulation was recapitulated in HEK 293 cells coexpressing the TrkB neurotrophin receptor. t-PA promoter-deletion analysis revealed the presence of two BDNF-responsive domains, one located between −3.07 and −2.5 kb and the other within the proximal promoter. The upstream region was shown to confer BDNF responsiveness in a TrkB-dependent manner when attached to a heterologous promoter. We also identify homologous regions within the murine and bovine t-PA gene promoters and demonstrate that the equivalent upstream murine sequence functions as a BDNF-responsive enhancer when inserted 5' of the human proximal t-PA promoter. Hence, BDNF-mediated induction of t-PA transcription relies on conserved modular promoter elements including a novel upstream BDNF-responsive domain and the proximal t-PA gene promoter.
Subject headings
- MEDICIN OCH HÄLSOVETENSKAP -- Medicinska och farmaceutiska grundvetenskaper -- Cell- och molekylärbiologi (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Basic Medicine -- Cell and Molecular Biology (hsv//eng)
Keyword
- Animals
- Base Sequence
- Brain-Derived Neurotrophic Factor
- chemistry
- metabolism
- physiology
- Cattle
- Cell Line
- Cell Line
- Tumor
- Conserved Sequence
- Enhancer Elements (Genetics)
- physiology
- Gene Expression Regulation
- Enzymologic
- physiology
- Genes
- Reporter
- Humans
- Mice
- Molecular Sequence Data
- Neurons
- enzymology
- metabolism
- Promoter Regions (Genetics)
- Tissue Plasminogen Activator
- chemistry
- genetics
- physiology
Publication and Content Type
- ref (subject category)
- art (subject category)
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