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PDRG1 at the interface between intermediary metabolism and oncogenesis

World Journal of Biological Chemistry 2017年第4期8卷 175-186页

作者： Maríaángeles Pajares Department of Chemical and Physical Biology Centro de Investigaciones Biológicas(CSIC)Madrid 28040Spain Instituto de Investigación Sanitaria La Paz(IdiPAZ) Madrid 28046Spain

PDRG1 is a small oncogenic protein of 133 residues. In normal human tissues, the p53 and DNA damageregulated gene 1(PDRG1) gene exhibits maximal expression in the testis and minimal levels in the liver. Increased expression has been detected in several tumor cells and in response to genotoxic stress. High-throughput studies identified the PDRG1 protein in a variety of macromolecular complexes involved in processes that are altered in cancer cells. For example, this oncogene has been found as part of the RNA polymerase Ⅱ complex, the splicing machinery and nutrient sensing machinery, although its role in these complexes remains unclear. More recently, the PDRG1 protein was found as an interaction target for the catalytic subunits of methionine adenosyltransferases. These enzymes synthesize S-adenosylmethionine, the methyl donor for, among others, epigenetic methylations that occur on the DNA and histones. In fact, downregulation of S-adenosylmethionine synthesis is the first functional effect directly ascribed to PDRG1. The existence of global DNA hypomethylation, together with increased PDRG1 expression, in many tumor cells highlights the importance of this interaction as one of the putative underlying causes for cell transformation. Here, we will review the accumulated knowledge on this oncogene, emphasizing the numerous aspects that remain to be explored.

关键词： Epigenetic modifications Glutathione Methylation Oncogenes Intermediary metabolism p53 and DNA damage-regulated gene 1 Protein complexes R2TP/prefoldin complex S-adenosylmethionine synthesis redox stress

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