WDR74 functions as a novel coactivator in TGF-β signaling.

Smads are critical intracellular signal transducers for transforming growth factor-β (TGF-β) in mammalian cells. In this study, we have identified WD repeat-containing protein 74 (WDR74) as a novel transcriptional coactivator for Smads in the canonical TGF-β signaling pathway. Through direct interactions with Smad proteins, WDR74 enhances TGF-β-mediated phosphorylation and nuclear accumulation of Smad2 and Smad3. Consequently, WDR74 enables stronger transcriptional responses and more robust TGF-β-induced physiological responses. Our findings have elucidated a critical role of WDR74 in regulating TGF-β signaling.