Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:4.1.99.3 (PRE)
 1,923 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Decay-accelerating factor (DAF) expression modulates susceptibility of cells to autologous complement attack. To characterize the regulatory region controlling DAF gene transcription, genomic DNA extending from 815 base pairs (bp) upstream to approximately 4 kilobases downstream of DAF's AUG codon (designated +1) was cloned and sequenced. The 5' flanking sequence showed 59-76% G + C content (-355 to +1), at least one GC box(es) (-135 to -131), and variable length sequences (from -629 to -285) conforming to the motifs TCCTCC and TCn. Nuclease S1 digestions and primer extensions localized a major transcriptional start site to -82/-81, 38 bp downstream of a possible TATA variant, (A)TTTAA. In COS cell transfections, the sequence encompassing -815 to -67 functioned 2.5% as efficiently as the Rous sarcoma virus 3' long terminal repeat, but following deletion upstream of -355 its activity increased approximately 4-fold. Two octanucleotides exhibiting partial homology to phorbol 12-myristate 13-acetate (PMA) and cAMP responsive elements (PREs and CREs, respectively) were detected, and the respective modulators enhanced transcriptional efficiency 2- and approximately 10-fold, respectively. Thus, the DAF gene promoter (i) exhibits sequences resembling both conventional and unconventional transcriptional control elements, (ii) possesses a region with negative regulatory activity, and (iii) responds to PMA and cAMP induction presumably via PRE- and CRE-like enhancer elements.
 ...
PMID:Characterization of the decay-accelerating factor gene promoter region. 171 Dec 8

The progesterone receptor (PR) is an important regulator of female reproduction. Consequently, PR modulators have found numerous pharmaceutical utilities in women's reproductive health. In the process of identifying more receptor-specific and tissue-selective PR modulators, we discovered a novel nonsteroidal, 6-aryl benzoxazinone compound, PRA-910, that displays unique in vitro and in vivo activities. In a PR/PRE reporter assay in COS-7 cells, PRA-910 shows potent PR antagonist activity with an IC50 value of approximately 20 nM. In the alkaline phosphatase assay in the human breast cancer cell line T47D, PRA-910 is a partial progesterone antagonist at low concentrations and is also an effective PR agonist at higher concentrations (EC50 value of approximately 700 nM). PRA-910 binds to the human PR with high affinity (Kd = 4 nM) and was previously shown to exhibit greater than 100-fold selectivity for the PR versus other steroid receptors. In the adult ovariectomized rat, PRA-910 is a potent PR antagonist. It inhibits progesterone-induced uterine decidual response with an ED50 value of 0.4 mg/kg, p.o., and reverses progesterone suppression of estradiol-induced complement C3 expression with potency similar to RU-486. In the nonhuman primate, however, PRA-910 is a PR agonist. The effect on endometrial histology strongly resembles that of progesterone. This unique compound also suppresses estradiol-induced epithelial cell proliferation and both estrogen and progesterone receptor expression in the uterine endometrium as a PR agonist would. In summary, PRA-910 is a structurally and biologically novel selective PR modulator with either PR agonist or antagonist activity, depending on context, concentration, and species.
 ...
PMID:In vitro and in vivo characterization of a novel nonsteroidal, species-specific progesterone receptor modulator, PRA-910. 1854 May 73

Hepatitis B virus (HBV) infection is a primary cause of hepatocellular carcinoma and liver cirrhosis worldwide. To develop novel antiviral drugs, a better understanding of HBV gene expression regulation is vital. One important aspect is to understand how HBV hijacks the cellular machinery to export unspliced RNA from the nucleus. The HBV post-transcriptional regulatory element (HBV PRE) has been proposed to be the HBV RNA nuclear export element. However, the function remains controversial, and the core element is unclear. This study, therefore, aimed to identify functional regulatory elements within the HBV PRE and investigate their functions. Using bioinformatics programs based on sequence conservation and conserved RNA secondary structures, three regulatory elements were predicted, namely PRE 1151-1410, PRE 1520-1620 and PRE 1650-1684. PRE 1151-1410 significantly increased intronless and unspliced luciferase activity in both HepG2 and COS-7 cells. Likewise, PRE 1151-1410 significantly elevated intronless and unspliced HBV surface transcripts in liver cancer cells. Moreover, motif analysis predicted that PRE 1151-1410 contains several regulatory motifs. This study reported the roles of PRE 1151-1410 in intronless transcript nuclear export and the splicing mechanism. Additionally, these results provide knowledge in the field of HBV RNA regulation. Moreover, PRE 1151-1410 may be used to enhance the expression of other mRNAs in intronless reporter plasmids.
...
PMID:A conserved RNA structural element within the hepatitis B virus post-transcriptional regulatory element enhance nuclear export of intronless transcripts and repress the splicing mechanism. 2651 43