title: Posttranslational Regulation of Smads.
abstract: Transforming growth factor β (TGF-β) family signaling dictates highly complex programs of gene expression responses, which are extensively regulated at multiple levels and vary depending on the physiological context. The formation, activation, and destruction of two major functional complexes in the TGF-β signaling pathway (i.e., the TGF-β receptor complexes and the Smad complexes that act as central mediators of TGF-β signaling) are direct targets for posttranslational regulation. Dysfunction of these complexes often leads or contributes to pathogenesis in cancer and fibrosis and in cardiovascular, and autoimmune diseases. Here we discuss recent insights into the roles of posttranslational modifications in the functions of the receptor-activated Smads in the common Smad4 and inhibitory Smads, and in the control of the physiological responses to TGF-β. It is now evident that these modifications act as decisive factors in defining the intensity and versatility of TGF-β responsiveness. Thus, the characterization of posttranslational modifications of Smads not only sheds light on how TGF-β controls physiological and pathological processes but may also guide us to manipulate the TGF-β responses for therapeutic benefits.
authors.affiliation: Life Sciences Institute and Innovation Center for Cell Signaling Network, Zhejiang University, Hangzhou, Zhejiang 310058, China.
authors.forename: Pinglong
authors.initials: P
authors.lastname: Xu
authors.affiliation: Michael E. DeBakey Department of Surgery, Baylor College of Medicine, Houston, Texas 77030.
authors.forename: Xia
authors.initials: X
authors.lastname: Lin
authors.affiliation: Life Sciences Institute and Innovation Center for Cell Signaling Network, Zhejiang University, Hangzhou, Zhejiang 310058, China.|Michael E. DeBakey Department of Surgery, Baylor College of Medicine, Houston, Texas 77030.|Department of Molecular & Cellular Biology, Baylor College of Medicine, Houston, Texas 77030.
authors.forename: Xin-Hua
authors.initials: XH
authors.lastname: Feng
mesh_terms: D000818:Animals; D006801:Humans; D010766:Phosphorylation; D011499:Protein Processing, Post-Translational; D051785:Smad Proteins / Q000378:metabolism*
chemical_list: D051785:Smad Proteins