Abstract
TGF-β(transforming growth factor-β) superfamily signaling mediators are important regulators of diverse physiological and pathological events. TGF-β signals are transduced by transmembrane type I and type II serine/threonine kinase receptors and their downstream effectors, the SMAD (drosophila mothers against decapentaplegic protein) proteins. Numerous studies have already demonstrated crucial regulatory roles for modification of TGF-β pathway components by poly-ubiquitination. Recently, several studies also uncovered mono-ubiquitination of SMADs as a mechanism for SMAD activation or inactivation. Mono-ubiquitination and subsequent deubiquitination of SMAD proteins accordingly play important roles in the control of TGF-β superfamily signaling. This review highlights the major pathways regulated by SMAD mono-ubiquitination.
Highlights
The SMAD proteins are part of the signaling cascades that represent the canonical downstream pathways of transforming growth factor β (TGF-β) super family proteins, which include TGF-βs, Activins, Inhibins, BMPs, GDFs, and Nodal
SMAD3 is poly-ubiquitinated by carboxyl terminus of Hsc70-interacting protein (CHIP) [31], and SMAD7 has been shown to be targeted for poly-ubiquitination by ARKADIA and RNF12 [32,33,34]
In line with the role of SMAD4 as common-partner, FAM/Usp9x was identified as an SMAD4 deubiquitinating enzyme (DUB) that is critical for both TGF-β and BMP responsiveness in human cells and Xenopus embryos
Summary
The SMAD proteins are part of the signaling cascades that represent the canonical downstream pathways of transforming growth factor β (TGF-β) super family proteins, which include TGF-βs, Cells 2014, 3. Homology (MH) and MH2 domains, respectively, which are connected by a less conserved linker region Both the MH1 and MH2 domains mediate interactions of SMADs with other transcription factors, co-activators, co-repressors and chromatin-remodeling factors. Nodal proteins are essential for mesoderm induction in vertebrates [3,4,5,6]; BMP signals are essential for embryonic patterning and early skeletal formation [7]; TGF-β/Activin regulates vascular function and angiogenesis due to their promotion of both EMT (epithelial to mesenchymal transition) and EndoMT (endothelial to mesenchymal transition) [8,9]. It can inhibit cell cycle progression or induce apoptosis and, thereby, be cytostatic or cytotoxic in premalignant tumor cells. For information on other types of regulation and receptor-initiated Non-SMAD signaling, we refer to two recent review articles [12,13]
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
