ATP-dependent RNA helicase DDX18 (DDX18)

ATP-dependent RNA helicase DDX18 is a member of the DEAD-box protein family, characterized by the conserved Asp-Glu-Ala-Asp (DEAD) motif. DDX18 functions primarily as an RNA helicase, unwinding RNA secondary structures in an ATP-dependent manner and playing a crucial role in diverse RNA metabolic processes such as translation initiation, splicing, and ribosome and spliceosome assembly. It is essential for the regulation of ribosome biogenesis and cell proliferation and is activated by the Myc protein. DDX18 is necessary for embryonic stem cell pluripotency, acting to preserve rDNA chromatin structure and prevent repressive chromatin modifications. Loss of DDX18 function can induce p53-dependent G1 cell cycle arrest and apoptosis, highlighting its role in cell survival and hematopoiesis. Overexpression and dysfunction of DDX18 have been implicated in several cancer types, where it serves as a key downstream effector of oncogenic signaling pathways and promotes aggressive tumor behavior. DDX18 also plays a role in viral infection, such as promoting replication of porcine reproductive and respiratory syndrome virus (PRRSV) by interacting with viral nonstructural proteins and facilitating viral propagation. Current evidence does not list approved or investigational drugs directly targeting DDX18, nor detailed mechanisms of action or safety data for DDX18 inhibitors. DDX18’s identification as a hub gene and overexpression in cancers suggest potential as a biomarker or therapeutic target, but clinical translation remains to be established.

Other names

Has1MRDBDEAD box protein 18DEAD (Asp-Glu-Ala-Asp) box polypeptide 18Myc-regulated DEAD box proteinHelicase Associated with Set1 homolog (S. cerevisiae)