Controlling Smad4 signaling with a Wip

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.