%0 Journal Article
%T Transcriptional cofactors Ski and SnoN are major regulators of the TGF-¦Â/Smad signaling pathway in health and disease
%J -
%D 2018
%R https://doi.org/10.1038/s41392-018-0015-8
%X The transforming growth factor-¦Â (TGF-¦Â) family plays major pleiotropic roles by regulating many physiological processes in development and tissue homeostasis. The TGF-¦Â signaling pathway outcome relies on the control of the spatial and temporal expression of >500 genes, which depend on the functions of the Smad protein along with those of diverse modulators of this signaling pathway, such as transcriptional factors and cofactors. Ski (Sloan-Kettering Institute) and SnoN (Ski novel) are Smad-interacting proteins that negatively regulate the TGF-¦Â signaling pathway by disrupting the formation of R-Smad/Smad4 complexes, as well as by inhibiting Smad association with the p300/CBP coactivators. The Ski and SnoN transcriptional cofactors recruit diverse corepressors and histone deacetylases to repress gene transcription. The TGF-¦Â/Smad pathway and coregulators Ski and SnoN clearly regulate each other through several positive and negative feedback mechanisms. Thus, these cross-regulatory processes finely modify the TGF-¦Â signaling outcome as they control the magnitude and duration of the TGF-¦Â signals. As a result, any alteration in these regulatory mechanisms may lead to disease development. Therefore, the design of targeted therapies to exert tight control of the levels of negative modulators of the TGF-¦Â pathway, such as Ski and SnoN, is critical to restore cell homeostasis under the specific pathological conditions in which these cofactors are deregulated, such as fibrosis and cancer
%U https://www.nature.com/articles/s41392-018-0015-8