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Traf2 interacts with Smad4 and regulates BMP signaling pathway in MC3T3-E1 osteoblasts.

Abstract：

:Bone morphogenetic proteins (BMPs) play important roles in osteoblast differentiation and maturation. In mammals, the BMP-induced receptor-regulated Smads form complexes with Smad4. These complexes translocate and accumulate in the nucleus, where they regulate the transcription of various target genes. However, the function of Smad4 remains unclear. We performed a yeast two-hybrid screen using Smad4 as bait and a cDNA library derived from bone marrow, to indentify the proteins interacting with Smad4. cDNA clones for Tumor necrosis factor (TNF) receptor-associated factor 2 (Traf2) were identified, and the interaction between the endogenous proteins was confirmed in the mouse osteoblast cell line MC3T3-E1. To investigate the function of Traf2, we silenced it with siRNA. The level of BMP-2 protein in the medium, the expression levels of the Bmp2 gene and BMP-induced transcription factor genes, including Runx2, Dlx5, Msx2, and Sp7, and the phosphorylated-Smad1 protein level were increased in cells transfected with Traf2 siRNA. The nuclear accumulation of Smad1 increased with TNF-alpha stimulation for 30 min at Traf2 silencing. These results suggest that the TNF-alpha-stimulated nuclear accumulation of Smad1 may be dependent on Traf2. Thus, the interaction between Traf2 and Smad4 may play a role in the cross-talk between TNF-alpha and BMP signaling pathways.

journal_name

Biochem Biophys Res Commun

journal_title

Biochemical and biophysical research communications

authors

Shimada K,Ikeda K,Ito K

doi

10.1016/j.bbrc.2009.10.048

subject

Has Abstract

pub_date

2009-12-18 00:00:00

pages

775-9

issue

3

eissn

0006-291X

issn

1090-2104

pii

S0006-291X(09)02026-9

journal_volume

390

pub_type

杂志文章

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