Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.1.30.1 (S1 nuclease)
 3,660 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The involvement of platelets and the c-mpl receptor in the regulation of thrombopoietin (TPO) plasma concentrations and tissue mRNA levels was investigated in both normal mice and mice defective in c-mpl (c-mpl-/-). Although c-mpl-/- mice have fewer platelets and higher plasma TPO activity than normal mice, there was no increase in TPO mRNA levels as measured by an S1 nuclease protection assay. After the intravenous injection of 125I-TPO, specific uptake of radioactivity by the spleen and blood cells was present in the normal mice, but absent in the c-mpl-/- mice. Platelet-rich plasma (PRP) from normal mice was able to bind and internalize 125I-TPO, whereas PRP from c-mpl-/- mice lacked this ability. Analysis of 125I-TPO binding to normal PRP indicated that binding was specific and saturable, with an approximate affinity of 560 pmol/L and 220 receptors per platelet. PRP from normal mice was also able to degrade 125I-TPO into lower molecular weight fragments. After the intravenous injections, c-mpl-/- mice cleared a dose of 125I-TPO at a much slower rate than did normal mice. Injection of washed platelets from normal mice into c-mpl-/- mice resulted in a dramatic, but transient, decrease in plasma TPO levels. These data provide evidence that platelets regulate plasma TPO levels via binding to the c-mpl receptor on circulating platelets.
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PMID:Regulation of thrombopoietin levels by c-mpl-mediated binding to platelets. 973 Oct 84

Thrombopoietin (TPO) is predominantly expressed in the liver among various tissues that express TPO transcripts. To investigate the transcriptional regulation of the human TPO gene in the liver, we determined the major transcription initiation site by means of 5'-RACE and Northern blotting. From these analyses, we concluded that TPO gene transcription started at various points, and the transcription initiation sites of the human TPO gene were localized downstream, close to a point we determined by S1 nuclease mapping. The human TPO promoter region contains consensus sequences of GATA, Evi-1, and Ets binding sites. We used the hepatocellular carcinoma cell line, HepG2, that expresses TPO mRNA to analyze its promoter activity by transfecting various reporter plasmids containing a sequentially 5'-deleted human TPO promoter. Although GATA binding factors increased the promoter activity, their effect was independent of the GATA binding consensus sequence. On the other hand, Evi-1 did not affect transcription. Moreover, we defined the core promoter region, in which an Ets binding consensus sequence was located. The deletion or mutation of the Ets binding site resulted in a loss of the promoter activity. These results suggested that TPO is regulated by the Ets family of transcription factors.
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PMID:Gene expression and transcriptional regulation of thrombopoietin. 1101 15