DEAH-box helicase 33 (DHX33)

DEAH-box helicase 33 (DHX33) is a nucleolar ATP-dependent RNA helicase that plays a critical role in ribosome biogenesis by promoting the transcription of ribosomal RNA (rRNA) and the assembly of ribosomal subunits. Beyond its role in the nucleolus, DHX33 is involved in mRNA translation and has been identified as a cytosolic sensor for double-stranded RNA, leading to the activation of the NLRP3 inflammasome. In the context of oncology, DHX33 is frequently overexpressed in various malignancies, including glioblastoma, lung cancer, and hepatocellular carcinoma, where it drives cell proliferation and survival by meeting the high demand for protein synthesis. Because its expression is often low in normal resting cells but high in rapidly dividing tumor cells, it is considered a promising therapeutic target for cancer treatment. While specific small-molecule inhibitors are currently in the early stages of discovery and development, targeting DHX33 aims to selectively disrupt the metabolic machinery of cancer cells. However, therapeutic strategies must carefully manage potential toxicities related to the fundamental biological processes DHX33 mediates in healthy tissues.

Other names

DHX33DDX33DEAH box protein 33ATP-dependent RNA helicase DHX33Nucleolar RNA helicase

Inhibition of ATP-dependent RNA helicase activity to disrupt ribosome biogenesis and protein synthesis in rapidly dividing cancer cells.