, Volume 347, Issue 1, pp 21-36
Date: 04 Jun 2011

Role of Smads in TGFβ signaling

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Abstract

Transforming growth factor-β (TGFβ) is the prototype for a large family of pleiotropic factors that signal via heterotetrameric complexes of type I and type II serine/threonine kinase receptors. Important intracellular mediators of TGFβ signaling are members of the Smad family. Smad2 and 3 are activated by C-terminal receptor-mediated phosphorylation, whereafter they form complexes with Smad4 and are translocated to the nucleus where they, in cooperation with other transcription factors, co-activators and co-repressors, regulate the transcription of specific genes. Smads have key roles in exerting TGFβ-induced programs leading to cell growth arrest and epithelial-mesenchymal transition. The activity and stability of Smad molecules are carefully regulated by a plethora of post-translational modifications, including phosphorylation, ubiquitination, sumoylation, acetylation and poly(ADP)-ribosylation. The Smad function has been shown to be perturbed in certain diseases such as cancer.

The authors acknowledge funding by the Ludwig Institute for Cancer Research, the Swedish Cancer Society, the Swedish Research Council and the Network of Excellence “ENFIN” under the European Union FP6 program.