Journal
ACTA BIOCHIMICA ET BIOPHYSICA SINICA
Volume 50, Issue 1, Pages 37-50Publisher
OXFORD UNIV PRESS
DOI: 10.1093/abbs/gmx129
Keywords
TGF-beta; Smad; signaling regulation; feedback loop; context
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Funding
- National Natural Science Foundation of China (NSFC) [31671460, 31401198]
- Natural Science Foundation of Jiangxi Province of China [20171ACB21004]
- NSFC [81760509, 31330049]
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Transforming growth factor beta (TGF-beta) 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-beta 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-beta/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-beta signaling, and then discuss how each step of TGF-beta signaling is finely controlled by distinct modes of feedback mechanisms, involving both protein regulators and miRNAs.
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