Department Cell and Chemical Biology, Oncode Institute, Leiden University Medical Center, Leiden, The Netherlands.
EMBO Rep. 2020 May 6;21(5):e50246. doi: 10.15252/embr.202050246. Epub 2020 Mar 18.
Members of the transforming growth factor-β (TGF-β) family play key roles in embryogenesis and in maintaining tissue homeostasis, and their perturbation can result in a broad range of diseases. One way TGF-β family signaling pathways are kept in check is by reversible (de)phosphorylation of intracellular Smad effectors. In this issue of EMBO Reports, Park et al [1] identify the phosphatase wild-type p53-induced phosphatase 1 (Wip1) as a negative regulator of TGF-β family signaling. Mechanistically, Wip1 constrains TGF-β family signaling through direct dephosphorylation of Thr277, an activating MAP kinase phosphorylation site located in the linker region of the common mediator Smad4.
转化生长因子-β（TGF-β）家族成员在胚胎发生和组织稳态维持中发挥着关键作用，它们的紊乱可能导致广泛的疾病。TGF-β 家族信号通路受到调控的一种方式是通过细胞内 Smad 效应物的可逆（去）磷酸化。在本期的《EMBO 报告》中，Park 等人[1]确定磷酸酶野生型 p53 诱导的磷酸酶 1（Wip1）是 TGF-β 家族信号的负调节剂。从机制上讲，Wip1 通过直接去磷酸化位于共同介质 Smad4 连接区的激活 MAP 激酶磷酸化位点 Thr277 来限制 TGF-β 家族信号。
