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:3.1.4.1 (
phosphodiesterase
)
18,767
document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)
Phosphodiesterase 3A (PDE3A), a member of the cGMP-inhibited cyclic nucleotide phosphodiesterase (
PDE
) family, plays important roles in oocyte maturation and vascular smooth muscle cell proliferation. However, the molecular mechanisms that regulate
PDE3A
gene expression remain largely unknown. In this study, we investigated the transcriptional regulation of
PDE3A
, and found that the splicing factor proline and glutamine rich (SFPQ) protein modulated
PDE3A
mRNA levels. Multiple transcription start sites (TSS1, 2, and 3) were identified within the first exon of
PDE3A
using 5'-rapid amplification of cDNA ends (RACE). Variable expression levels of three
PDE3A
variants were also observed in human tissues and HeLa cells. Several putative SFPQ-binding sites were identified upstream of the regulatory region of
PDE3A
-TSSs using chromatin immunoprecipitation sequencing (ChIP-seq). Serum-induced
PDE3A
expression was affected by increasing the amount of SFPQ binding to the upstream regulatory region of
PDE3A
In addition, transcription of
PDE3A
was lower in human
cervical adenocarcinoma
cells compared to normal cervical tissue. Furthermore, over-expression of
PDE3A
induced sensitivity to anti-cancer therapeutic agent, 6-(4-(diethylamino)-3-nitrophenyl)-5-methyl-4,5-dihydropyridazin-3(2H)-one (DNMDP), in HeLa cells. Taken together, these results suggest that SFPQ functions as a transcriptional activator of
PDE3A,
which is involved in the regulation of DNMDP sensitivity
,
offering a novel molecular target for the development of anticancer therapies.
...
PMID:SFPQ, a multifunctional nuclear protein, regulates the transcription of
PDE3A
. 2874 36
