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)
Interferons (IFNs alpha, beta and gamma) and all trans retinoic acid (RA) have the ability to activate genes with
GAS
sites. We have found that the promoter of
CD26
/
dipeptidylpeptidase IV
(
DPPIV
) contains a consensus
GAS
site TTCnnnGAA located at bp-35 to -27, and computer analysis confirmed this sequence to be a putative Stat binding site. Consistent with this finding, we show that IFNs and RA rapidly enhanced
CD26
gene and protein expression in chronic B lymphocytic leukemia (B-CLL) cells. Immunoblot analyses revealed that unstimulated B-CLL cells expressed detectable levels of serine/tyrosine-phosphorylated Stat1alpha, and RA and IFN-gamma treatment led to increased levels of tyrosine phosphorylation of Stat1alpha and its nuclear accumulation. As shown by electrophoretic mobility shift assay, RA and IFN-gamma increased the binding of a nuclear protein to the
GAS
-
CD26
element. Shift-Western blotting identified Stat1alpha as the
GAS
-
CD26
binding factor. Augmented levels of
CD26
protein in malignant B cells cultured with IFNs or RA coincided with the enhancement of
DPPIV
activity. Taken together, our results are in favor of the IFN-/RA-mediated upregulation of
CD26
/
DPPIV
in B-CLL through the signaling pathway involving Stat1alpha and the
GAS
response element of
CD26
promoter.
...
PMID:Regulation of CD26/DPPIV gene expression by interferons and retinoic acid in tumor B cells. 1064 5
