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)

Analogs of amaninamide, due to the absence of a 6-hydroxy group in the tryptophan moiety, are more easily accessible by synthesis than derivatives of alpha-amanitin. Syntheses of bicyclic octapeptide thioethers 1f-1m have been carried out starting from linear Hpi-S-trityl-octapeptides (3), cyclization by intramolecular 2'-indolylthioether formation yielding monocyclic peptides (2) and final cyclization by DCCI. One of the bicyclic thioethers was oxidized to yield the corresponding chromatographically separated (R)- and (S)-sulfoxides, respectively. The products were characterized by RF-values, u.v. and CD spectra as well as by mass (FAB) spectroscopy. The widely differing inhibitory activities on RNA polymerase II (or B) from calf thymus are listed.
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PMID:Synthesis of analogues of amaninamide, an amatoxin from the white Amanita virosa mushroom. 342 28

Ile3-amaninamide (3-R) and its diastereomeric sulfoxide (3-S) are obtained by oxidation of the bicyclic thioether peptide 2 by hydrogen peroxide in acetic acid. 2 was prepared by an intramolecular Savige-Fontana reaction of the linear octapeptide tert.-butylester 4 whose N-terminal Boc-Hpi residue on treatment with TFA loses the Boc group and reacts under thioether formation with the released cysteine-SH. The concomitantly deprotected carboxyl terminus is coupled intramolecularly with the free amino group of the secocompound 5 using the MA or DCCI method, thus forming the homodetic peptide ring. Compounds 3-R and 3-S agree very well with analog samples in chiroptical behavior. Thioether 2 and sulfoxide 3-R exert 50% inhibition of RNA polymerase II (or B) from Drosophila melanogaster in 10(-6) M solution whereas Ki of 3-S is about five times higher.
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PMID:Analogs of amanin. Synthesis of Ile3-amaninamide and its diastereoisomeric (S)-sulfoxide. 679 36

The present study was undertaken to define the gene(s) of importance on the long arm of chromosome 18 (chromosome 18q) in endometrial carcinomas. We analyzed loss of heterozygosity (LOH) at 3 loci on chromosome 18q and DCC gene expression by the reverse-transcriptase/polymerase chain reaction (RT-PCR) method. Among 61 tumors that were informative, 16 (26%), estimated to be a minimum number, showed allelic losses at one or more chromosome 18q loci. Deletions in these tumors possibly involved the region within or near the chromosome 18q 21.3 band where the DCC gene was localized. Moreover, the incidence of altered DCC mRNA expression was high in these tumors. Appropriate transcription was lost in 5 of 7 (71%) carcinoma cell lines in addition to 14 of 28 (50%) surgically resected tumors. Histopathological differentiation and clinical stage of disease were not related to LOH frequency or to DCC mRNA expression. These results suggest that the target for allelic loss on chromosome 18q seen in endometrial carcinomas is the DCC gene, and that inactivation of this gene may be critical for the development of most endometrial carcinomas.
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PMID:DCC gene alteration in human endometrial carcinomas. 751 50

In many human colorectal cancers, the DCC gene encoding for a homologue of the neural cell adhesion molecule (N-CAM) is found to be deleted. Previous work suggested that gap junctional intercellular communication (GJIC) might play an important role in carcinogenesis and could be regulated by the expression of cell adhesion molecules such as E-cadherin in some epithelial cell systems. In order to examine whether the deletion of the putative cell adhesion molecule DCC is related to the level of GJIC, which might, in turn, be important in human colorectal cancers, we compared levels of expression of the DCC gene with the GJIC capacity of a panel of human colorectal adenocarcinoma cell lines isolated from different stages of tumor progression. While the level of GJIC varied between the cell lines studied, we found no correlation between their communication capacity and DCC expression revealed by a reverse-transcriptase/polymerase chain reaction method. This lack of correlation suggests that DCC is not a crucial regulator of GJIC.
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PMID:Lack of correlation between the gap junctional communication capacity of human colon cancer cell lines and expression of the DCC gene, a homologue of a cell adhesion molecule (N-CAM). 839 66

The DCC (deleted in colorectal cancer) gene was originally identified as a candidate tumour suppressor gene in colon carcinogenesis on the basis of allelic losses in chromosome 18q.21 in 70% of colon cancers. Reverse transcriptase polymerase chain reaction (RT-PCR) of DCC mRNA suggests that DCC expression may also be reduced in colon cancers. We have used monoclonal antibodies generated against the DCC immunoglobulin-like domain to investigate DCC isoforms and DCC protein expression during colon cancer progression. Normal mucosa and colonic tumour specimens representative of the range of colonic tumour progression from benign adenomatous polyps to metastases were compared by Western blot analyses. We show that while M(r) 194 000 DCC is present in normal colonic mucosa and adenomatous polyps, it is also similarly expressed in colorectal carcinomas and colonic metastases in the liver. The presence of DCC protein is consistent with the presence of DCC mRNA transcripts in the same tissue specimens. Notably DCC was not completely lost in any colonic tumour specimens examined, even those that had progressed to metastatic cancers. Quantitation of DCC protein expression in tissue specimens by densitometry demonstrated that both normal and malignant specimens exhibit a wide range of DCC protein levels and there was no significant correlation between diminished DCC protein expression and colon cancer progression. These results demonstrate the pattern of expression of the DCC gene product in colonic tumour progression and show that absence of DCC expression is not associated with colonic tumour progression.
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PMID:The deleted in colon cancer (DCC) gene is consistently expressed in colorectal cancers and metastases. 876

One of the loci for neuroblastoma suppressor genes is chromosome 18q21 where the DPC4 tumor suppressor gene, as well as the DCC and MADR2 genes, is located. DPC4 is a molecule of the TGF-beta signal which regulates differentiation of the neural crest precursor cells from which neuroblastoma originates. During the search for the significance of DPC4 as a candidate neuroblastoma suppressor gene, we found that there are at least two variant forms of the DPC4 transcripts by using the reverse-transcriptase-PCR procedure. The subsequent sequencing analysis has revealed that one is missing exons 5 and 6 and the other is missing exons 4-6. Both splice variants were frequently observed in neuroblastomas and at low levels in normal tissues. Though the functional role of the DPC4 splice variants is unknown, they might be important in regulating the TGF-beta signaling not only in neuroblastomas but also in other tumors and normal tissues.
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PMID:DPC4 splice variants in neuroblastoma. 946 9