PMID- 17419735
OWN - NLM
STAT- MEDLINE
DCOM- 20070620
LR  - 20081121
IS  - 1742-464X (Print)
IS  - 1742-464X (Linking)
VI  - 274
IP  - 9
DP  - 2007 May
TI  - Two conserved regions within the tissue-type plasminogen activator gene promoter 
      mediate regulation by brain-derived neurotrophic factor.
PG  - 2411-23
AB  - 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.
FAU - Daniel, Philip B
AU  - Daniel PB
AD  - Monash University, Australian Centre for Blood Diseases, Melbourne, Australia.
FAU - Lux, Wolfram
AU  - Lux W
FAU - Samson, Andre L
AU  - Samson AL
FAU - Schleuning, Wolf-Dieter
AU  - Schleuning WD
FAU - Niego, Be'eri
AU  - Niego B
FAU - Weiss, Thomas W
AU  - Weiss TW
FAU - Tjarnlund-Wolf, Anna
AU  - Tjarnlund-Wolf A
FAU - Medcalf, Robert L
AU  - Medcalf RL
LA  - eng
PT  - Comparative Study
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20070405
PL  - England
TA  - FEBS J
JT  - The FEBS journal
JID - 101229646
RN  - 0 (Brain-Derived Neurotrophic Factor)
RN  - EC 3.4.21.68 (Tissue Plasminogen Activator)
SB  - IM
MH  - Animals
MH  - Base Sequence
MH  - Brain-Derived Neurotrophic Factor/*chemistry/*metabolism/physiology
MH  - Cattle
MH  - Cell Line
MH  - Cell Line, Tumor
MH  - *Conserved Sequence
MH  - Enhancer Elements, Genetic/physiology
MH  - Gene Expression Regulation, Enzymologic/*physiology
MH  - Genes, Reporter
MH  - Humans
MH  - Mice
MH  - Molecular Sequence Data
MH  - Neurons/enzymology/metabolism
MH  - *Promoter Regions, Genetic
MH  - Tissue Plasminogen Activator/*chemistry/*genetics/physiology
EDAT- 2007/04/11 09:00
MHDA- 2007/06/21 09:00
CRDT- 2007/04/11 09:00
PHST- 2007/04/11 09:00 [pubmed]
PHST- 2007/06/21 09:00 [medline]
PHST- 2007/04/11 09:00 [entrez]
AID - EJB5777 [pii]
AID - 10.1111/j.1742-4658.2007.05777.x [doi]
PST - ppublish
SO  - FEBS J. 2007 May;274(9):2411-23. doi: 10.1111/j.1742-4658.2007.05777.x. Epub 2007 
      Apr 5.