Structural determinants of Smad function in TGF-β signaling Journal Article
| Authors: | Macias, M. J.; Martin-Malpartida, P.; Massagué, J. |
| Article Title: | Structural determinants of Smad function in TGF-β signaling |
| Abstract: | Smad transcription factors are central to the signal transduction pathway that mediates the numerous effects of the transforming growth factor β (TGF-β) superfamily of cytokines in metazoan embryo development as well as in adult tissue regeneration and homeostasis. Although Smad proteins are conserved, recent genome-sequencing projects have revealed their sequence variation in metazoan evolution, human polymorphisms, and cancer. Structural studies of Smads bound to partner proteins and target DNA provide a framework for understanding the significance of these evolutionary and pathologic sequence variations. We synthesize the extant mutational and structural data to suggest how genetic variation in Smads may affect the structure, regulation, and function of these proteins. We also present a web application that compares Smad sequences and displays Smad protein structures and their disease-associated variants. © 2015 Elsevier Ltd. |
| Keywords: | signal transduction; somatic mutation; review; nonhuman; pancreas cancer; protein domain; protein function; metastasis; smad protein; smad1 protein; smad2 protein; smad3 protein; smad5 protein; smad7 protein; transforming growth factor beta; protein dna binding; protein protein interaction; genetic variability; cancer inhibition; sequence alignment; cancer cell; smad proteins; negative feedback; protein structure; point mutation; nonsense mutation; metazoa; metastatic melanoma; smad4 protein; human; priority journal; cancer mutations; smad conservation/variation; smad dna binding; smad structure; smad-binding proteins; tgf-β signaling |
| Journal Title: | Trends in Biochemical Sciences |
| Volume: | 40 |
| Issue: | 6 |
| ISSN: | 0968-0004 |
| Publisher: | Elsevier Inc. |
| Date Published: | 2015-06-01 |
| Start Page: | 296 |
| End Page: | 308 |
| Language: | English |
| DOI: | 10.1016/j.tibs.2015.03.012 |
| PROVIDER: | scopus |
| PUBMED: | 25935112 |
| PMCID: | PMC4485443 |
| DOI/URL: | |
| Notes: | Export Date: 3 June 2015 -- Source: Scopus |
