DEAD-box helicase 3 X-linked (DDX3X) (DDX3X)

DEAD-box helicase 3 X-linked (DDX3X) is a multifunctional ATP-dependent RNA helicase belonging to the DEAD-box protein family [4, 9]. It plays a central role in nearly all aspects of RNA metabolism, including transcription, pre-mRNA splicing, mRNA export, and translation initiation, particularly for mRNAs with complex 5' untranslated regions [11, 12]. Beyond its core RNA-processing functions, DDX3X is a key regulator of cellular signaling pathways such as Wnt/beta-catenin and NF-kappaB, and it is involved in the formation of stress granules and the innate immune response [5, 10, 18]. In oncology, DDX3X is frequently overexpressed and acts as an oncogene in various cancers, including breast, colorectal, and glioblastoma, where it promotes cell proliferation and metastasis [1, 13, 15]. Conversely, it can act as a tumor suppressor in certain contexts, such as in some cases of hepatocellular carcinoma [25, 27]. DDX3X is also a critical host factor for the replication of numerous viruses, including HIV-1, HCV, and SARS-CoV-2, making it a promising target for broad-spectrum antiviral therapy [6, 10, 29]. Small molecule inhibitors like RK-33 and BA103 are being developed to target its ATPase or helicase activities to treat cancer and viral infections [1, 31].

Other names

DDX3DBXHLP2DDX14CAP-RfMRX102MRXSSBDEAD-box polypeptide 3 X-linkedATP-dependent RNA helicase DDX3X

Inhibition of the ATP-binding site (ATPase activity) or the RNA-binding site (helicase activity), leading to suppressed mRNA translation of oncogenic proteins, disruption of Wnt/beta-catenin signaling, and induction of the innate immune response [1, 13, 15, 30].