Fig. 1

As a TF co-activator and an RNA helicase, DDX5 (p68) has diverse functions to act as an oncogenic master regulator: A DDX5-mediated transcriptional activation of many oncogenic genes by interacting with different TFs (e.g., c-Myc) together with CDK9/cyclin T1 complex, which bridges basic transcription machinery on the oncogene promoters; B DDX5 regulation of mRNA stability by interacting with RNA stability modulators (e.g., interacting with the IGF2BPs complex); C DDX5-regulated DNA conformational changes. This is achieved (i) through interaction with various topoisomerases (TOPs) to alter DNA topological structure, and (ii) through interaction with toposome (e.g., interacting with topoisomerase 2α-containing complex) for chromosome segregation; D DDX5 interaction with DNA repair regulators (Table 1) and involvement in DNA repair and genome surveillance. For example, DDX5 participates in NHEJ DNA repair by interacting with NF45/NF90 and Ku70/Ku80 complexes, and DDX5 participates in NER and facilitates DNA repair by interacting with replication factor C (RFC) proteins; E DDX5 regulation of the splicing of pre-RNA, microRNA (miRNA) and circular RNA (circRNA; e.g., Wang et al., Aging US 2023, 15:2525–40); and F DDX5 regulation of ribosome biogenesis through interacting with other regulators such as nucleophosmin 1 (NPM1) on the ribosomal DNA promoter. Note: The diverse functions of DDX5 presented herein were based on many literature reports but primarily based on the recent publication from Le et al., Mol Ther 2023 Feb 1; 31(2):471–486