Poster abstracts
Poster number 128 submitted by Zheng Cindy Xing
Characterization of the mammalian DEAD-box protein DDX5 reveals functional conservation with S. cerevisiae ortholog Dbp2 in transcriptional control and glucose metabolism
Zheng Xing (Department of Biochemistry, Purdue University), Siwen Wang (Department of Biochemistry, Purdue University), Elizabeth Tran (Department of Biochemistry, Purdue Center for Cancer Research, Purdue University)
Abstract:
DEAD-box proteins are a class of non-processive RNA helicases that dynamically modulate the structure of RNA and ribonucleoprotein complexes (RNPs). However, the precise roles of individual members are not well understood. Work from our lab revealed that the DEAD-box protein Dbp2 in Saccharomyces cerevisiae is an active RNA helicase in vitro that functions in transcription by promoting mRNP assembly, repressing cryptic transcription initiation, and regulating long non-coding RNA activity. Interestingly, Dbp2 is also linked to glucose sensing and hexose transporter gene expression. DDX5 is the mammalian ortholog of Dbp2 that has been implicated in cancer and metabolic syndrome, suggesting that the role of Dbp2 and DDX5 in glucose metabolic regulation are conserved. Herein, we present a refined biochemical and biological comparison of yeast Dbp2 and human DDX5 enzymes. We find that human DDX5 possesses a 10-fold higher unwinding activity than Dbp2, which is partially due to the presence of a mammalian/avian specific C-terminal extension. Interestingly, ectopic expression of DDX5 rescues the cold sensitivity, cryptic initiation defects, and impaired glucose import in dbp2∆ cells, suggesting functional conservation. Consistently, we show that DDX5 promotes glucose uptake and glycolysis in mammalian cells, a process that is upregulated in cancers. We will present evidence that DDX5 may be a novel entry point for therapeutic targeting of cancer-specific metabolism.
Keywords: DEAD-box helicase , Glycolysis