SPSB1, a novel negative regulator of the TGF-beta signaling pathway targeting the type II receptor
- Author(s)
- Liu, S; Nheu, T; Luwor, R; Nicholson, SE; Zhu, HJ;
- Details
- Publication Year 2016-07-17,Volume 290,Issue #29,Page 17894-17908
- Journal Title
- Journal of Biological Chemistry
- Publication Type
- Journal Article
- Abstract
- Appropriate cellular signaling is essential to control cell proliferation, differentiation and cell death. Aberrant signaling can have devastating consequences and lead to disease states including cancer. The transforming growth factor-beta (TGF-beta) signaling pathway is a prominent signaling pathway that has been tightly regulated in normal cells while its deregulation strongly correlates with the progression of human cancers. The regulation of the TGF-beta signaling pathway involves a variety of physiological regulators. Many of these molecules act to alter the activity of Smad proteins. In contrast, the number of molecules known to affect TGF-beta signaling pathway at the receptor level is relatively low and there are no known direct modulators for the TGF-beta type II receptor (TbetaRII). Here we identify SPSB1 (a SPRY domain-containing SOCS box protein) as a novel regulator of the TGF-beta signaling pathway. SPSB1 negatively regulates TGF-beta signaling pathway through its interaction with both endogenous and over-expressed TbetaRII (and not TbetaRI) via its SPRY domain. As such, TbetaRII and SPSB1 colocalize on the cell membrane. SPSB1 maintains TbetaRII at a low level by enhancing the ubiquitination levels and degradation rates of TbetaRII through its SOCS box. More importantly, silencing SPSB1 by siRNA results in enhanced TGF-beta signaling and migration and invasion of tumor cells.
- Publisher
- ASMB
- Research Division(s)
- Inflammation; Systems Biology And Personalised Medicine
- PubMed ID
- 26032413
- Publisher's Version
- https://doi.org/10.1074/jbc.M114.607184
- Terms of Use/Rights Notice
- Refer to copyright notice on published article.
Creation Date: 2015-06-15 09:53:28
Last Modified: 2016-05-05 11:03:01