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Blood, 15 January 2008, Vol. 111, No. 2, pp. 885-893. Prepublished online as a Blood First Edition Paper on October 10, 2007; DOI 10.1182/blood-2007-03-082941. This Article Full Text Full Text (PDF) Supplemental Material Supplemental Figures All Versions of this Article: blood-2007-03-082941v1 111/2/885    most recent Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Rights and Permissions Citing Articles Citing Articles via HighWire Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by Lee, Y. Articles by Kim, H.-H. Search for Related Content PubMed PubMed Citation Articles by Lee, Y. Articles by Kim, H.-H. Related Collections Phagocytes Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  PHAGOCYTES The ubiquitin-mediated degradation of Jak1 modulates osteoclastogenesis by limiting interferon-β–induced inhibitory signaling Youngkyun Lee1, Seok-Won Hyung2, Hee Jung Jung2, Hyung-Joon Kim1, Judith Staerk3, Stefan N. Constantinescu3, Eun-Ju Chang1, Zang Hee Lee1, Sang-Won Lee2, and Hong-Hee Kim1 1 Department of Cell and Developmental Biology, BK21 Program, Dental Research Institute (DRI), School of Dentistry, Seoul National University, Seoul, Korea; 2 Department of Chemistry, Korea University, Seoul, Korea; and 3 Ludwig Institute for Cancer Research, Brussels, Belgium Interferons (IFNs) have been shown to negatively regulate osteoclastogenesis. In a proteomic study to assess protein expression during osteoclastogenesis, we discovered that the expression level of Jak1 was significantly decreased during the early stage of osteoclast differentiation from mouse bone marrow macrophages (BMMs) upon stimulation with receptor activator of nuclear factor B ligand (RANKL). RANKL induced Jak1 ubiquitination, and a proteasome inhibitor MG132 efficiently blocked the RANKL-induced degradation of Jak1. The expression level of Jak1 correlated with the susceptibility of osteoclast precursors to the negative regulatory effects of IFN-β on osteoclastogenesis, since preosteoclasts (pOCs) in which Jak1 expression is significantly reduced could proceed with osteoclastogenesis in the presence of IFN-β. Forced down-regulation of Jak1 by small interfering RNA (siRNA) resulted in the efficient osteoclast differentiation of BMMs in the presence of inhibitory IFN-β, while overexpression of Jak1 in pOCs elicited IFN-β–dependent inhibition of osteoclastogenesis. Furthermore, we found that the IFN-β–induced inhibition of osteoclastogenesis required STAT3 downstream of Jak1. These data suggest that the regulation of Jak1 expression during osteoclast differentiation might serve as an intrinsic mechanism that determines osteoclast lineage commitment by modulating the negative regulation by IFN-β. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: Y. Lee, J. Ha, H. J. Kim, Y.-S. Kim, E.-J. Chang, W.-J. Song, and H.-H. Kim Negative Feedback Inhibition of NFATc1 by DYRK1A Regulates Bone Homeostasis J. Biol. Chem., November 27, 2009; 284(48): 33343 - 33351. [Abstract] [Full Text] [PDF]

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