Transcriptional cofactors Ski and SnoN are major regulators of the TGF-β/Smad signaling pathway in health and disease

• DOI: 10.1038/s41392-018-0015-8
• Publication Date: 2018-05-31T17:03:08Z
• Authors: Angeles C. Tecalc...; Diana G. Ríos-López; Genaro Vázquez-Vi...; Reyna E. Rosales-...; Marina Macías-Silva
• Keywords: 0303 health sciences; 03 medical and health sciences; Review Article; 3. Good health

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