Multi-talented DEAD-box proteins and potential tumor promoters: p68 RNA helicase (DDX5) and its paralog, p72 RNA helicase (DDX17).

Janknecht, Ralf

P68 (DDX5) and p72 (DDX17) are members of the DEAD-box RNA helicase family. They can unwind double-stranded RNA and also contribute to the remodeling of ribonucleoprotein complexes. These activities of p68/p72 are required for efficient RNA splicing and microRNA processing. In addition, p68/p72 perform functions that are independent of their enzymatic activity. This is especially common to their role in gene regulation, where p68/p72 coactivate various transcription factors, including the tumor suppressor p53, estrogen receptor alpha and beta-catenin. P68/p72 are posttranslationally modified by SUMO attachment and phosphorylation that regulate their coactivation potential, binding to known interactants or protein stability. Knock-out mouse models revealed that both DDX5 and DDX17 are essential genes during development. Furthermore, together with their ability to stimulate cell proliferation and prevent apoptosis, the reported overexpression of p68/p72 in three of the major human cancers (colon, breast, prostate) strongly suggests that p68/p72 promote tumorigenesis and might even represent proto-oncoproteins. If so, their inhibition holds promise as a novel way to contain or cure various carcinomas.