PDRG1 at the interface between intermediary metabolism and oncogenesis

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.

Chlamydomonas WDR92 in association with R2TP-like complex and multiple DNAAFs to regulate ciliary dynein preassembly

The motility of cilia or eukaryotic flagella is powered by the axonemal dyneins,which are preassembled in the cytoplasm by proteins termed dynein arm assembly factors(DNAAFs)before being transported to and assembled on the ciliary axoneme.Here,we characterize the function of WDR92 in Chlamydomonas.Loss of WDR92,a cytoplasmic protein,in a mutant wdr92 generated by DNA insertional mutagenesis resulted in aflagellate cells or cells with stumpy or short flagella,disappearance of axonemal dynein arms,and diminishment of dynein arm heavy chains in the cytoplasm,suggesting that WDR92 is a DNAAF.Immunoprecipitation of WDR92 followed by mass spectrometry identified inner dynein arm heavy chains and multiple DNAAFs including RuvBLl,RPAP3,MOT48,ODA7,and DYX1C.The PIH1 domain-containing protein MOT48 formed a R2TP-like complex with RuvBLl/2 and RPAP3,while PF13,another PIH1 domain-containing protein with function in dynein preassembly,did not.Interestingly,the third PIH1 domain-containing protein TWI1 was not related to flagellar motility.WDR92 physically interacted with the R2TP-like complex and the other identified DNNAFs.Our data suggest that WDR92 functions in association with the HSP90 co-chaperone R2TP-like complex as well as linking other DNAAFs in dynein preassembly.