MOE Key Laboratory of Biosystems Homeostasis & Protection and Innovation Center for Cell Signaling Network, Life Sciences Institute, Zhejiang University, Hangzhou 310058, China; Department of Biochemistry and Molecular Biology, University of Texas Health Science Center at Houston, Houston, TX 77030, USA.
MOE Key Laboratory of Biosystems Homeostasis & Protection and Innovation Center for Cell Signaling Network, Life Sciences Institute, Zhejiang University, Hangzhou 310058, China.
J Genet Genomics. 2018 Dec 20;45(12):639-650. doi: 10.1016/j.jgg.2018.08.005. Epub 2018 Nov 27.
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 是哺乳动物细胞中转化生长因子-β (TGF-β) 的关键细胞内信号转导蛋白。在这项研究中，我们鉴定出 WD 重复蛋白 74（WDR74）是经典 TGF-β 信号通路中 Smads 的新型转录共激活因子。通过与 Smad 蛋白的直接相互作用，WDR74 增强了 Smad2 和 Smad3 的 TGF-β 介导的磷酸化和核积累。因此，WDR74 能够实现更强的转录反应和更稳健的 TGF-β 诱导的生理反应。我们的研究结果阐明了 WDR74 在调节 TGF-β 信号中的关键作用。
