Publications
Detailed Information
Phospho-Smad1 Modulation by Nedd4 E3 Ligase in BMP/TGF-beta Signaling
DC Field | Value | Language |
---|---|---|
dc.contributor.author | Kim, Byung-Gyu | - |
dc.contributor.author | Lee, Ji-Hyun | - |
dc.contributor.author | Yasuda, Jiro | - |
dc.contributor.author | Ryoo, Hyun-Mo | - |
dc.contributor.author | Cho, Je-Yoel | - |
dc.date.accessioned | 2013-01-15T00:45:36Z | - |
dc.date.available | 2013-01-15T00:45:36Z | - |
dc.date.issued | 2011-07 | - |
dc.identifier.citation | JOURNAL OF BONE AND MINERAL RESEARCH, Vol.26 No.7, pp.1411-1424 | ko_KR |
dc.identifier.issn | 0884-0431 | - |
dc.identifier.uri | https://hdl.handle.net/10371/80539 | - |
dc.description.abstract | A considerable number of studies have focused on the regulation of mothers against decapentaplegic homologue (Smad)-dependent or -independent pathways in the signaling by each transforming growth factor beta (TGF-beta) superfamily member in diverse biologic contexts. The sophisticated regulation of the actions of these molecules and the underlying molecular mechanisms still remain elusive. Here we show new mechanisms of ambilateral R (receptor-regulated)-Smad regulation of bone morphogenetic protein 2 (BMP-2)/TGF-beta 1 signals. In a specific context, both signals regulate the nonclassic Smads pathway reciprocally, BMP-2 to Smad2/3 and TGF-beta 1 to Smad1/5/8, as well as their own classic linear Smad pathway. Interestingly, in this study, we found that C-terminal phosphorylated forms of each pathway Smad degraded rapidly 3 hours after stimulation of nonclassic signals but are dramatically restored by treatment with via proteasomal inhibition. Furthermore, an E3 ligase, neural precursor cell expressed, developmentally down-regulated 4 (Nedd4), also was found as one of the important modulators of the p-Smad1 in both BMP-2 and TGF-beta 1 action. Overexpressed Nedd4 suppressed the BMP-induced osteoblast transdifferentiation process of premyoblast C2C12 cells or alkaline phosphatase (ALP) level of human osteosarcoma cells and promoted TGF-beta 1-induced degradation of p-Smad1 via physical interaction and polyubiquitination. Conversely, siNedd4 potentiated BMP signals through upregulation of p-Smad1 and ALP activity, the effect of which led to an increased the rate of Pi-induced calcification of human vascular smooth muscle cells. These new insights about proteasomal degradation-mediated phosphorylated nonclassic Smad regulation of BMP-2/TGF-beta 1 could, in part, help to unravel the complex mechanisms of abnormal nonosseous calcification by the aberrant activity of BMPTTGF-beta/Smads. (C) 2011 American Society for Bone and Mineral Research. | ko_KR |
dc.language.iso | en | ko_KR |
dc.publisher | WILEY-BLACKWELL | ko_KR |
dc.subject | NONOSSEOUS CALCIFICATION | ko_KR |
dc.subject | BMP/TGF beta | ko_KR |
dc.subject | NEDD4 | ko_KR |
dc.subject | SMAD | ko_KR |
dc.title | Phospho-Smad1 Modulation by Nedd4 E3 Ligase in BMP/TGF-beta Signaling | ko_KR |
dc.type | Article | ko_KR |
dc.contributor.AlternativeAuthor | 김병규 | - |
dc.contributor.AlternativeAuthor | 이지현 | - |
dc.contributor.AlternativeAuthor | 류현모 | - |
dc.contributor.AlternativeAuthor | 조제열 | - |
dc.identifier.doi | 10.1002/jbmr.348 | - |
dc.citation.journaltitle | JOURNAL OF BONE AND MINERAL RESEARCH | - |
dc.description.tc | 1 | - |
- Appears in Collections:
- Files in This Item:
- There are no files associated with this item.
Item View & Download Count
Items in S-Space are protected by copyright, with all rights reserved, unless otherwise indicated.