Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
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

p11 is expressed in many different cell types, and serves a variety of regulatory functions. In order to better understand the transcriptional control of this protein, the 5' promoter region of the human p11 gene was cloned and sequenced. After confirming the transcription start point (TSP) using 5' rapid amplification of cDNA ends analysis, the 5' promoter was analysed. The sequence lacks a TATA box, but contains a variety of putative regulatory elements. There are two GAS sites, two AP-1 sites, two overlapping Sp-1 sites, and a gamma-IRE site clustered between -1080 and -1450. There is another cluster of putative regulatory sites between the TSP and -550 which contains two Sp-1 sites, two AP-2 sites, one GAS site, one NF-kappaB site, an incomplete CAAT box (8/9) and an overlapping Sp-1/AP-2 site at -17 to -26. Reporter gene constructs containing 4225 and 1498 bases 5' of the TSP demonstrated excellent unidirectional transcriptional activity in both constructs. Reporter genes containing serial 5' deletions were compared to the -1498 construct. The reporter gene which contained base pairs (bp) -36 to +89 had almost no activity. The reporter gene containing -188 to +89 had 50% of the -1498 construct, indicating that this sequence contains at least the minimal promoter. The Sp-1/AP-2 site near the transcription start site was studied by electrophoretic mobility shift and reporter gene assays. Addition of HeLa cell nuclear extract to labeled double-stranded (ds) oligonucleotide containing this sequence resulted in a gel shift which was inhibited by excess unlabeled ds oligonucleotide and by a consensus cold Sp-1 ds oligonucleotide, indicating specific Sp-1 binding. Excess AP-2 or NF-kappaB ds oligonucleotide had no effect on nuclear protein binding to the sequence. Mutation of the p11 wild-type Sp-1/AP-2 sequence eliminated both nuclear protein binding and the sequences ability to compete with native sequence for nuclear binding protein. A -1048 to +89 reporter construct containing a mutated Sp-1/AP-2 site resulted in a 40% decrease in transcriptional activity. Therefore, the 5' flanking sequence of the p11 gene exhibits promoter activity which may be localized to a variety of controlling regions, of which the proximal Sp-1/AP-2 site appears to be important for basal activity via its Sp-1 binding ability.
 ...
PMID:Characterization of the human p11 promoter sequence. 1280 40