Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:2.7.7.6 (RNA polymerase)
 34,946 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

To study the relative expression of lactase, sucrase-isomaltase, dipeptidyl peptidase IV, and the Na(+)-dependent glucose transporter mRNA transcripts in small samples of human tissue, we have developed and validated a very simple semiquantitative RNA polymerase chain reaction method that can be used on as little as 5-10 mg of tissue. Here we report the use of this method to study the expression of these genes at different stages of development, in different tissues and in different parts of the intestine, in comparison with another intestinal marker, the colon-specific transcript of carbonic anhydrase 1. Lactase, sucrase-isomaltase, and the Na(+)-dependent glucose transporter mRNA are expressed predominantly in the small intestine, although lactase mRNA is expressed at a very low level in fetuses. Dipeptidyl peptidase IV mRNA shows a much wider tissue distribution. Sucrase-isomaltase and dipeptidyl peptidase IV mRNA are present at high levels in fetal colon and also at surprisingly high levels in adult colon. Lactase mRNA, on the other hand, is present at very low levels in fetal colon and is not detectable at all in adult colon. The Na(+)-dependent glucose transporter mRNA in contrast is expressed at higher levels in the adult colon than in the fetal colon. This is also the case for the carbonic anhydrase 1 transcript, although this transcript is not expressed in the small intestine. Thus, each of these genes shows different developmental and cell-specific regulation.
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PMID:Expression of human intestinal mRNA transcripts during development: analysis by a semiquantitative RNA polymerase chain reaction method. 781 28

Fibroblast activation protein (FAP) is a cell surface-bound protease of the prolyl oligopeptidase gene family expressed at sites of tissue remodelling. This study aimed to delineate the expression of FAP in cirrhotic human liver and examine its biochemical activities. Seventeen cirrhotic and 8 normal liver samples were examined by immunohistochemistry and reverse-transcriptase polymerase chain reaction (RT-PCR). Hepatic stellate cells (HSC) were isolated and immunostained. Recombinant FAP and immunopurified, natural FAP were analyzed for protease activities and similarities to dipeptidyl peptidase IV (DPPIV), a structurally related enzyme. FAP-specific messenger RNA and immunoreactivity were detected in cirrhotic, but not normal, livers. FAP immunoreactivity was most intense on perisinusoidal cells of the periseptal regions within regenerative nodules (15 of 15 cases); this pattern coincides with the tissue remodelling interface. In addition, human FAP was expressed by cells within the fibrous septa (10 of 15 cases). Cell morphology, location, and colocalization with glial fibrillary acidic protein (GFAP) indicated that FAP is present on HSC in vivo. Similarly, isolated HSC expressed FAP in vitro. Both natural FAP from cirrhotic liver and recombinant FAP were shown to have gelatinase and dipeptidyl peptidase activities. FAP is a cell-bound, dual-specificity dipeptidyl peptidase and gelatinase expressed by activated HSC at the tissue remodelling interface in human cirrhosis. FAP may contribute to the HSC-induced extracellular matrix (ECM) changes of cirrhosis.
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PMID:Fibroblast activation protein: a cell surface dipeptidyl peptidase and gelatinase expressed by stellate cells at the tissue remodelling interface in human cirrhosis. 1034 20

CD26 is a type II glycoprotein known as dipeptidyl peptidase IV and has been identified as one of the cell surface markers associated with various types of cancers and a subset of cancer stem cells. Recent studies have suggested that CD26 expression is involved in tumor growth, tumor invasion, and metastasis. The CD26 is shown in an extensive intracellular distribution, ranging from the cell surface to the nucleus. We have previously showed that the humanized anti-CD26 monoclonal antibody (mAb), YS110, exhibits inhibitory effects on various cancers. However, functions of CD26 on cancer cells and molecular mechanisms of impaired tumor growth by YS110 treatment are not well understood. In this study, we demonstrated that the treatment with YS110 induced nuclear translocation of both cell-surface CD26 and YS110 in cancer cells and xenografted tumor. It was shown that the CD26 and YS110 were co-localized in nucleus by immunoelectron microscopic analysis. In response to YS110 treatment, CD26 was translocated into the nucleus via caveolin-dependent endocytosis. It was revealed that the nuclear CD26 interacted with a genomic flanking region of the gene for POLR2A, a subunit of RNA polymerase II, using a chromatin immunoprecipitation assay. This interaction with nuclear CD26 and POLR2A gene consequently led to transcriptional repression of the POLR2A gene, resulting in retarded cell proliferation of cancer cells. Furthermore, the impaired nuclear transport of CD26 by treatment with an endocytosis inhibitor or expressions of deletion mutants of CD26 reversed the POLR2A repression induced by YS110 treatment. These findings reveal that the nuclear CD26 functions in the regulation of gene expression and tumor growth, and provide a novel mechanism of mAb-therapy related to inducible translocation of cell-surface target molecule into the nucleus.
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PMID:Nuclear localization of CD26 induced by a humanized monoclonal antibody inhibits tumor cell growth by modulating of POLR2A transcription. 2363 30