Molecular Biology of the Cell track citations

Home Help [Feedback] [For Subscribers] [Archive] [Search] --
QUICK SEARCH:   [advanced]


     

MBC in Press, published online ahead of print February 20, 2008
Mol. Biol. Cell 10.1091/mbc.E07-10-1057

A more recent version of this article appeared on May 1, 2008
This Article
Right arrow Full Text (PDF)
Right arrow All Versions of this Article:
E07-10-1057v1
19/5/2113    most recent
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrow reprints & permissions
Citing Articles
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Luan, Y.
Right arrow Articles by Liu, C.-j.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Luan, Y.
Right arrow Articles by Liu, C.-j.

Submitted on October 22, 2007
Revised on January 25, 2008
Accepted on February 13, 2008

p204 Protein Overcomes the Inhibition of Cbfa1-mediated Osteogenic Differentiation by Id Helix-Loop-Helix Proteins

Yi Luan,*{dagger} Xiu-Ping Yu,{dagger} Ning Yang,* Sally Frenkel,* Lin Chen,{ddagger} and Chuan-ju Liu*{sect}{dagger}

*Department of Orthopaedic Surgery, New York University School of Medicine, New York, NY, 10003; {sect}Department of Cell Biology, New York University School of Medicine, New York, NY 10016; {dagger}Institute of Pathogenic Biology, Shandong University School of Medicine, Jinan, Shandong 250012, China; {ddagger}State Key Laboratory of Trauma, Burns and Combined Injury, Trauma Center, Institute of Surgery Research, Daping Hospital, Third Military Medical University, Chongqing 400042, China

Monitoring Editor: William Tansey

Id proteins play important roles in osteogenic differentiation; however, the molecular mechanism remains unknown. In this study we established that Id proteins, including Id1, Id2 and Id3, associate with Cbfa1 to cause diminished transcription of the alkaline phosphatase (ALP) and osteocalcin (OCL) gene leading to less ALP activity and osteocalcin (OCL) production. Id acts by inhibiting the sequence-specific binding of Cbfa1 to DNA and by decreasing the expression of Cbfa1 in cells undergoing osteogenic differentiation. p204, an interferon-inducible protein that interacts with both Cbfa1 and Id2, overcame the Id2-mediated inhibition of Cbfa1-induced ALP activity and OCL production. We show that (1) p204 disturbed the binding of Id2 to Cbfa1 and enabled Cbfa1 to bind to the promoters of its target genes and (2) that p204 promoted the translocation from nucleus to the cytoplasm and accelerated the degradation of Id2 by ubiquitin-proteasome pathway during osteogenesis. Nucleus export signal (NES) of p204 is required for the p204-enhanced cytoplasmic translocation and degradation of Id2, since a p204 mutant lacking NES lost these activities. Take together, Cbfa1, p204 and Id proteins form a regulatory circuit and act in concert to regulate osteoblast differentiation.

Address correspondence to: Chuan-ju Liu (chuanju.liu{at}med.nyu.edu)






Home Help [Feedback] [For Subscribers] [Archive] [Search] --
Copyright © 2008 by The American Society for Cell Biology. Terms of copyright protection, warranties, and disclaimers.