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World J Biol Chem. Nov 26, 2017; 8(4): 175-186
Published online Nov 26, 2017. doi: 10.4331/wjbc.v8.i4.175
PDRG1 at the interface between intermediary metabolism and oncogenesis
María Ángeles Pajares
María Ángeles Pajares, Department of Chemical and Physical Biology, Centro de Investigaciones Biológicas (CSIC), Madrid 28040, Spain
María Ángeles Pajares, Instituto de Investigación Sanitaria La Paz (IdiPAZ), Madrid 28046, Spain
Author contributions: Pajares MÁ searched the literature, prepared the figures and wrote the paper.
Conflict-of-interest statement: The author declares no conflict of interest. The founding sponsors had no role in the design of the study; in the collection, analyses, or interpretation of data; in the writing of the manuscript, or in the decision to publish the results.
Open-Access: This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/
Correspondence to: María Ángeles Pajares, PhD, Senior Scientist, Senior Research Scientist, Department of Chemical and Physical Biology, Centro de Investigaciones Biológicas (CSIC), Ramiro de Maeztu 9, Madrid 28040, Spain. mapajares@cib.csic.es
Telephone: +34-91-8173112-4351 Fax: +34-91-5360432
Received: October 4, 2017
Peer-review started: October 6, 2017
First decision: October 30, 2017
Revised: November 14, 2017
Accepted: November 19, 2017
Article in press: November 20, 2017
Published online: November 26, 2017
Abstract

PDRG1 is a small oncogenic protein of 133 residues. In normal human tissues, the p53 and DNA damage-regulated 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.

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

Core tip: PDRG1 is an understudied protein of the R2TP/prefoldin-like complex that has been found as part of different multiprotein complexes. Increased PDRG1 expression levels have been associated with several types of tumors that concomitantly show global DNA hypomethylation. More recently, this protein has been uncovered as an interaction target for methionine adenosyltransferase catalytic subunits MATα1 and MATα2. Through this interaction, PDRG1 downregulates nuclear S-adenosylmethionine synthesis, hence impacting epigenetic methylations.