Cargando…
Transcriptional cofactors Ski and SnoN are major regulators of the TGF-β/Smad signaling pathway in health and disease
The transforming growth factor-β (TGF-β) family plays major pleiotropic roles by regulating many physiological processes in development and tissue homeostasis. The TGF-β signaling pathway outcome relies on the control of the spatial and temporal expression of >500 genes, which depend on the funct...
Autores principales: | , , , , |
---|---|
Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Nature Publishing Group UK
2018
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5992185/ https://www.ncbi.nlm.nih.gov/pubmed/29892481 http://dx.doi.org/10.1038/s41392-018-0015-8 |
_version_ | 1783329964704137216 |
---|---|
author | Tecalco-Cruz, Angeles C. Ríos-López, Diana G. Vázquez-Victorio, Genaro Rosales-Alvarez, Reyna E. Macías-Silva, Marina |
author_facet | Tecalco-Cruz, Angeles C. Ríos-López, Diana G. Vázquez-Victorio, Genaro Rosales-Alvarez, Reyna E. Macías-Silva, Marina |
author_sort | Tecalco-Cruz, Angeles C. |
collection | PubMed |
description | The transforming growth factor-β (TGF-β) family plays major pleiotropic roles by regulating many physiological processes in development and tissue homeostasis. The TGF-β 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-β 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-β/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-β signaling outcome as they control the magnitude and duration of the TGF-β 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-β 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. |
format | Online Article Text |
id | pubmed-5992185 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2018 |
publisher | Nature Publishing Group UK |
record_format | MEDLINE/PubMed |
spelling | pubmed-59921852018-06-11 Transcriptional cofactors Ski and SnoN are major regulators of the TGF-β/Smad signaling pathway in health and disease Tecalco-Cruz, Angeles C. Ríos-López, Diana G. Vázquez-Victorio, Genaro Rosales-Alvarez, Reyna E. Macías-Silva, Marina Signal Transduct Target Ther Review Article The transforming growth factor-β (TGF-β) family plays major pleiotropic roles by regulating many physiological processes in development and tissue homeostasis. The TGF-β 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-β 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-β/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-β signaling outcome as they control the magnitude and duration of the TGF-β 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-β 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. Nature Publishing Group UK 2018-06-08 /pmc/articles/PMC5992185/ /pubmed/29892481 http://dx.doi.org/10.1038/s41392-018-0015-8 Text en © The Author(s) 2018 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/. |
spellingShingle | Review Article Tecalco-Cruz, Angeles C. Ríos-López, Diana G. Vázquez-Victorio, Genaro Rosales-Alvarez, Reyna E. Macías-Silva, Marina Transcriptional cofactors Ski and SnoN are major regulators of the TGF-β/Smad signaling pathway in health and disease |
title | Transcriptional cofactors Ski and SnoN are major regulators of the TGF-β/Smad signaling pathway in health and disease |
title_full | Transcriptional cofactors Ski and SnoN are major regulators of the TGF-β/Smad signaling pathway in health and disease |
title_fullStr | Transcriptional cofactors Ski and SnoN are major regulators of the TGF-β/Smad signaling pathway in health and disease |
title_full_unstemmed | Transcriptional cofactors Ski and SnoN are major regulators of the TGF-β/Smad signaling pathway in health and disease |
title_short | Transcriptional cofactors Ski and SnoN are major regulators of the TGF-β/Smad signaling pathway in health and disease |
title_sort | transcriptional cofactors ski and snon are major regulators of the tgf-β/smad signaling pathway in health and disease |
topic | Review Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5992185/ https://www.ncbi.nlm.nih.gov/pubmed/29892481 http://dx.doi.org/10.1038/s41392-018-0015-8 |
work_keys_str_mv | AT tecalcocruzangelesc transcriptionalcofactorsskiandsnonaremajorregulatorsofthetgfbsmadsignalingpathwayinhealthanddisease AT rioslopezdianag transcriptionalcofactorsskiandsnonaremajorregulatorsofthetgfbsmadsignalingpathwayinhealthanddisease AT vazquezvictoriogenaro transcriptionalcofactorsskiandsnonaremajorregulatorsofthetgfbsmadsignalingpathwayinhealthanddisease AT rosalesalvarezreynae transcriptionalcofactorsskiandsnonaremajorregulatorsofthetgfbsmadsignalingpathwayinhealthanddisease AT maciassilvamarina transcriptionalcofactorsskiandsnonaremajorregulatorsofthetgfbsmadsignalingpathwayinhealthanddisease |