p68 (Ddx5) interacts with Runx2 and regulates osteoblast differentiation

Abstract

Runx2 is an essential transcription factor for osteoblast development from mesenchymal progenitors. Runx2 regulates gene expression by interacting with numerous transcription factors and co-activators to integrate signaling events within the nucleus. In this study we used affinity purification and proteomic techniques to identify novel Runx2 interacting proteins. One of these proteins is the DEAD box RNA helicase, p68 (Ddx5). p68 regulates many aspects of RNA expression, including transcription and splicing. p68 co-localized with Runx2 in punctate foci within the nucleus. In transcription assays, p68 functioned as a co-activator of Runx2, but its helicase activity was not essential for co-activation. In accordance, Runx2 transcriptional activity was muted in p68-suppressed cells. Surprisingly, osteoblast differentiation of the multipotent progenitor C2C12 cell line was accelerated by p68 suppression and Runx2 suppressed p68 expression in calvarial progenitor cells. Together these data demonstrate that p68 is a novel co-activator for Runx2, but it inhibits osteogenic differentiation of progenitor cells. Moreover Runx2 has an active role in regulating p68 levels in osteoblast precursors. Thus, crosstalk between Runx2 and p68 controls osteoblast specification and maturation at multiple levels.

DEAD box RNA helicase functions in cancer

“…Consistent with the idea that DDX5 has pro-proliferation or oncogenic roles in cancer, it has been shown to coactivate ERα, 97 Androgen Receptor (AR), 84 Runx2, 98 the NFκB transcription factor p50, 87 and to upregulate expression of cyclin D1, c-Myc consistent with β-catenin activation 88,91 as well as genes required for DNA replication. 96 Furthermore, DDX5 was found to activate transcription of the Snail1 gene by displacing histone deacetylase from the Snail1 promoter, 92 consistent with an involvement in EMT.…”

Interactome study suggests multiple cellular functions of hepatoma-derived growth factor (HDGF)

“…The DExD/H box proteins also play important roles in transcription, often as coactivators or corepressors through their interaction with key components of the transcriptional machinery [77]. For example, DDX5 and DDX17 have been shown to act as transcriptional co-activators for a diverse range of transcription factors, including ER alpha [78][79][80], the tumor suppressor p53 [81], the myogenic regulator MyoD [82,83] and Runx2 [84]. In some contexts, DDX5 and DDX17 can interact with HDAC1 and repress transcription as promoter-dependent transcriptional repressors [77,85].…”

Runx2 Regulates G Protein-coupled Signaling Pathways to Control Growth of Osteoblast Progenitors

“…1 and see Refs. [33][34][35][36]. For example, Runx2 interacts with GROUCHO/TLE proteins that require the conserved C-terminal VWRPY pentapeptide of Runx2 for gene repression (37).…”