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)

2',3'-Dideoxycytidine (ddC) is a nucleoside analogue and reverse-transcriptase inhibitor that is approved for treatment of AIDS patients. A rabbit model of ddC neurotoxicity was developed to help understand the dose-limiting clinical neurotoxicity of ddC. Rabbits with a myelinopathy resulting from treatment with ddC exhibited mitochondrial alterations in Schwann cells of sciatic and tibial nerves and dorsal root ganglia. These changes were initially evident after 16 weeks of oral treatment with 35 mg/kg per day of ddC and were positively correlated with myelin pathology in individual animals. Cup-shaped mitochondria were frequently observed; when these mitochondria occurred in multiple concentric arrays or at various angles to one another, different profiles were formed depending on the plane of section. An increased number of mitochondrial cristae assumed a tubular configuration. It is suggested that the complex aggregations of mitochondria seen in this experiment are an adaptive response to altered mitochondrial function caused by treatment with ddC.
 ...
PMID:Schwann cell mitochondrial alterations in peripheral nerves of rabbits treated with 2',3'-dideoxycytidine. 814 Aug 96

The Kruppel-like factor (KLF) proteins are multitasked transcriptional regulators with an expanding tumor suppressor function. KLF2 is one of the prominent members of the family because of its diminished expression in malignancies and its growth-inhibitory, pro-apoptotic and anti-angiogenic roles. In this study, we show that epigenetic silencing of KLF2 occurs in cancer cells through direct transcriptional repression mediated by the Polycomb group protein Enhancer of Zeste Homolog 2 (EZH2). Binding of EZH2 to the 5'-end of KLF2 is also associated with a gain of trimethylated lysine 27 histone H3 and a depletion of phosphorylated serine 2 of RNA polymerase. Upon depletion of EZH2 by RNA interference, short hairpin RNA or use of the small molecule 3-Deazaneplanocin A, the expression of KLF2 was restored. The transfection of KLF2 in cells with EZH2-associated silencing showed a significant anti-tumoral effect, both in culture and in xenografted nude mice. In this last setting, KLF2 transfection was also associated with decreased dissemination and lower mortality rate. In EZH2-depleted cells, which characteristically have lower tumorigenicity, the induction of KLF2 depletion 'rescued' partially the oncogenic phenotype, suggesting that KLF2 repression has an important role in EZH2 oncogenesis. Most importantly, the translation of the described results to human primary samples demonstrated that patients with prostate or breast tumors with low levels of KLF2 and high expression of EZH2 had a shorter overall survival.
 ...
PMID:Silencing of Kruppel-like factor 2 by the histone methyltransferase EZH2 in human cancer. 2189 11