摘要
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.
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.
基金
partly supported by the grants from National Natural Science Foundation of China (Nos. 31730057, 91540205, and 31571447)
National Basic Research Program of China (973 Program) (2015CB553803)
the Fundamental Research Funds for the Central Universities
