PURPOSE: To review the recent developments in the structure and function of Smad proteins. DATA SOURCES: Both Chinese- and English-language literatures were searched using MEDLINE/CD-ROM (1997 - 2000) and the Index of...PURPOSE: To review the recent developments in the structure and function of Smad proteins. DATA SOURCES: Both Chinese- and English-language literatures were searched using MEDLINE/CD-ROM (1997 - 2000) and the Index of Chinese-Language Literature (1997 - 2000). STUDY SELECTION: Data from published articles about TGF-beta signal transduction in recent domestic and foreign literature were selected. DATA EXTRACTION: Data were mainly extracted from 22 articles which are listed in the reference section of this review. RESULTS: Smad proteins mediate signal transduction induced by the TGF-beta superfamily. Based on their structural and functional properties, Smad proteins are divided into three groups. The first group, receptor-regulated Smads (R-Smads), are phosphorylated by activated type I receptors and form heteromeric complexes with the second group of Smads, common mediator Smads (Co-Smads). These Smad complexes translocate into the nucleus to influence gene transcription. Inhibitory Smads (I-Smads) are the third group and these antagonize the activity of R-Smads. In the nucleus, Smads can directly contact Smad-binding elements (SBE) in target gene promoters. Through interaction with different transcription factors, transcriptional co-activators or co-repressors, Smads elicit different effects in various cell types. The aberrance of Smad proteins has been noted in several human disorders such as fibrosis, hypertrophic scarring and cancer. CONCLUSION: The structure of Smads determines their function as transcriptional factors which translocate signals from the cell surface to the nucleus where Smads regulate TGF-beta superfamily-dependent gene expression.展开更多
Transforming growth factor-β (TGF-β) is a multifunctional peptide growth factor with a wide range of effects. TGF-β signals are conveyed through cell-surface serine/threonine kinase receptors to the downstream cyto...Transforming growth factor-β (TGF-β) is a multifunctional peptide growth factor with a wide range of effects. TGF-β signals are conveyed through cell-surface serine/threonine kinase receptors to the downstream cytoplasmic mediators, known as Smads proteins. Receptor-regulated Smads become phosphorylated by activated type Ⅰ receptors and form heteromeric complexes with a common Smad-Smad4, which translocates into the nucleus to regulate gene transcription. Inhibitory Smads inhibit the activation of receptor-regulated Smads. There are positive, negative and feedback regulations in the Smads mediated TGF-β signaling pathway.展开更多
基金supported by a grant from the National Natural Science Foundation of China(No．G1999054204)； the National Prominent Youth Science Foundation of China(No．39525024)．
文摘PURPOSE: To review the recent developments in the structure and function of Smad proteins. DATA SOURCES: Both Chinese- and English-language literatures were searched using MEDLINE/CD-ROM (1997 - 2000) and the Index of Chinese-Language Literature (1997 - 2000). STUDY SELECTION: Data from published articles about TGF-beta signal transduction in recent domestic and foreign literature were selected. DATA EXTRACTION: Data were mainly extracted from 22 articles which are listed in the reference section of this review. RESULTS: Smad proteins mediate signal transduction induced by the TGF-beta superfamily. Based on their structural and functional properties, Smad proteins are divided into three groups. The first group, receptor-regulated Smads (R-Smads), are phosphorylated by activated type I receptors and form heteromeric complexes with the second group of Smads, common mediator Smads (Co-Smads). These Smad complexes translocate into the nucleus to influence gene transcription. Inhibitory Smads (I-Smads) are the third group and these antagonize the activity of R-Smads. In the nucleus, Smads can directly contact Smad-binding elements (SBE) in target gene promoters. Through interaction with different transcription factors, transcriptional co-activators or co-repressors, Smads elicit different effects in various cell types. The aberrance of Smad proteins has been noted in several human disorders such as fibrosis, hypertrophic scarring and cancer. CONCLUSION: The structure of Smads determines their function as transcriptional factors which translocate signals from the cell surface to the nucleus where Smads regulate TGF-beta superfamily-dependent gene expression.
文摘Transforming growth factor-β (TGF-β) is a multifunctional peptide growth factor with a wide range of effects. TGF-β signals are conveyed through cell-surface serine/threonine kinase receptors to the downstream cytoplasmic mediators, known as Smads proteins. Receptor-regulated Smads become phosphorylated by activated type Ⅰ receptors and form heteromeric complexes with a common Smad-Smad4, which translocates into the nucleus to regulate gene transcription. Inhibitory Smads inhibit the activation of receptor-regulated Smads. There are positive, negative and feedback regulations in the Smads mediated TGF-β signaling pathway.
