Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Pivot Concepts:
Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Target Concepts:
Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Query: EC:4.2.3.23 (
GAS
)
957
document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)
We previously identified a 1.2 Kb DNA element (P-1161/+16), 5' to
caspase-8
exon-1, that acts as promoter in
caspase-8
-positive, but not in
caspase-8
-negative neuroblastoma (NB) cells. The P-1161/+16 DNA element regulates both constitutive and interferon IFN-gamma-inducible
caspase-8
expression. Two
GAS
(IFN-activated sequence, STAT-1 binding site) and two ISRE (interferon sensitive response element, IRF binding site) were present in P-1161/+16. Deletion studies indicated that elements essential for promoter activity in NB cells were present in a 167 bp region 5' flanking exon-1 (P-151/+16), which contains an ISRE at position -32. The transcription initiation site was mapped by 5' rapid amplification of cDNA end (RACE) at position -20 from
caspase-8
cDNA reference sequence. Disruption of the ISRE-32 indicated that it is required for both constitutive and IFN-gamma-inducible
caspase-8
expression. IRF-1 and IRF-2 transcription factors bind to the (-151/+16) DNA fragment in vitro. Chromatin immunoprecipitation (ChIP) assays showed that IRF-1 and IRF-2 bind to the DNA region at the 5' of
caspase-8
gene in NB cells, which show constitutive expression but not in
caspase-8
negative cells. In these last cells, up-regulation of
caspase-8
by IFN-gamma was associated to induction of IRF-1 and IRF-2 binding to
caspase-8
promoter and increased histone acetylation. Moreover, RNA interference experiments also supported the involvement of IRF-1 and IRF-2 in constitutive
caspase-8
expression in NB cells.
...
PMID:An interferon-sensitive response element is involved in constitutive caspase-8 gene expression in neuroblastoma cells. 1703 21
