Feedback regulation of TGF-β signaling. (8th December 2017)

• Record Type: Journal Article
• Authors: Yan, Xiaohua; Xiong, Xiangyang; Chen, Ye-Guang
• Is Part Of: Acta biochimica et biophysica Sinica. Volume 50:Number 1(2018:Jan.)
• Page Start: 37
• Page End: 50
• Publication Date: 2017-12-08
• Subjects: TGF-β -- Smad -- signaling regulation -- feedback loop -- context; Biochemistry -- Periodicals; Biophysics -- Periodicals; 572.05
• DOI: 10.1093/abbs/gmx129
• Languages: English
• ISSNs: 1672-9145

Abstract

Abstract: Transforming growth factor beta (TGF-β) is a multi-functional polypeptide that plays a critical role in regulating a broad range of cellular functions and physiological processes. Signaling is initiated when TGF-β ligands bind to two types of cell membrane receptors with intrinsic Ser/Thr kinase activity and transmitted by the intracellular Smad proteins, which act as transcription factors to regulate gene expression in the nucleus. Although it is relatively simple and straight-forward, this TGF-β/Smad pathway is regulated by various feedback loops at different levels, including the ligand, the receptor, Smads and transcription, and is thus fine-tuned in terms of signaling robustness, duration, specificity, and plasticity. The precise control gives rise to versatile and context-dependent pathophysiological functions. In this review, we firstly give an overview of TGF-β signaling, and then discuss how each step of TGF-β signaling is finely controlled by distinct modes of feedback mechanisms, involving both protein regulators and miRNAs.