Jun activation domain–binding protein 1 binds Smad5 and inhibits bone morphogenetic protein signaling
Article first published online: 28 NOV 2006
Copyright © 2006 by the American College of Rheumatology
Arthritis & Rheumatism
Volume 54, Issue 12, pages 3878–3884, December 2006
How to Cite
Haag, J. and Aigner, T. (2006), Jun activation domain–binding protein 1 binds Smad5 and inhibits bone morphogenetic protein signaling. Arthritis & Rheumatism, 54: 3878–3884. doi: 10.1002/art.22261
- Issue published online: 28 NOV 2006
- Article first published online: 28 NOV 2006
- Manuscript Accepted: 30 AUG 2006
- Manuscript Received: 16 JUN 2006
- German Federal Ministry of Education and Research. Grant Number: BMBF grant 01GG9824
Bone morphogenetic proteins (BMPs) play an important role in the development and the homeostasis and pathology of cartilage tissue, particularly in the differentiation and anabolic activity of chondrocytes. The present study was undertaken to identify binding partners of the Smad proteins, the intracellular mediators of BMP activity, which might actively modify BMP signaling in chondrocytes.
Yeast 2-hybrid technology was used to screen a complementary DNA library, constructed from human adult articular cartilage, for molecular binding partners of Smad5, a major intracellular mediator of BMP signaling. Primary interaction partners were verified by coimmunoprecipitation, and the relevance of the interactions to BMP signaling was evaluated by transcriptional reporter assay. Additionally, messenger RNA expression analysis (conventional and quantitative polymerase chain reaction) and immunostaining were performed in adult normal and osteoarthritic articular cartilage.
We identified a novel Smad5 interactor, Jun activation domain–binding protein 1 (Jab1), expressed in adult cartilage. The interaction was confirmed in coimmunoprecipitation experiments. Overexpression of Jab1 resulted in an attenuation of BMP-dependent transcriptional responses, suggesting that Jab1 acts as an inhibitor of BMP signaling.
Jab1 is a newly identified intracellular (negative) modulator of BMP signaling in chondrocytes and other cells. Jab1 represents an interesting molecule for understanding anabolic signaling in chondrocytes, as well as a potential therapeutic target for anabolic activation. Most interestingly, Jab1 appears to crosslink the BMP and interleukin-1 pathways.