Inhibitory machinery for the TGF-β family signaling pathway

Abstract

Transforming growth factor-β (TGF-β) family signaling regulates cell growth and differentiation of many different cell types and is widely involved in the regulation of homeostasis during both embryogenesis and adult life. Therefore, aberrant TGF-β family signal transduction is linked to congenital disorders, tumorigenicity, and fibrosis, which can be life-threatening. A specific receptor–ligand complex initiates transduction of TGF-β family signaling to the nucleus via intracellular signal molecules, mainly Smads, whereby a number of bioactivities such as wound healing, immunomodulation, apoptosis, and angiogenesis are controlled. To avoid an excess of TGF-β family signaling in cells, the duration and intensity of the TGF-β family signal appear to be subject to elaborate regulation. In this paper, we describe recent advances in the understanding of how TGF-β family signals are perturbed and terminated to maintain homeostasis in cells.

Keywords::

• miRNA
• phosphatase
• proteasomes
• Smad
• TMEPAI
• ubiquitin

Acknowledgements

We thank Ms F. Miyamasu for excellent English proofreading.

Declaration of interest: Our work was supported by grants from Grants-in-aid for Scientific Research (21590328) (S.I.) from the Ministry of Education, Culture, Sports, Science, and Technology of Japan; the Takeda Science Foundation (S.I.); and the Naito Foundation (S.I.). The authors report no conflicts of interest. The authors alone are responsible for the content and writing of the paper.