Article abstract
Nature Cell Biology 9, 287 - 298 (2007)
Published online: 18 February 2007 | doi:10.1038/ncb1538
Constitutive RelA activation mediated by Nkx3.2 controls chondrocyte viability
Minsun Park1,3, Yeryoung Yong1,3, Seung-Won Choi1, Jae Hwan Kim2, Jong Eun Lee2 & Dae-Won Kim1
Abstract
During endochondral ossification, a process that accounts for the majority of bone formation in vertebrates, hypertrophic chondrocytes display a greater susceptibility to apoptosis when compared to proliferating chondrocytes. However, the molecular mechanisms underlying this phenomenon remain unclear. Nkx3.2, a member of the NK class of homeoproteins, is initially expressed in chondrogenic precursor cells, and later, during cartilage maturation, its expression is restricted to proliferating chondrocytes. Here, we show that the nuclear factor kappa B (NF-
B) pathway is required for chondrocyte viability and that Nkx3.2 supports chondrocyte survival by constitutively activating RelA. Although signal-dependent NF-B activation has been intensively studied, ligand-independent NF-B activation is poorly understood. The data presented here support a novel ligand-independent mechanism of NF-B activation, whereby Nkx3.2 recruits the RelA–IB
heteromeric complex into the nucleus by direct protein–protein interactions and activates RelA through proteasome-dependent IB degradation in the nucleus. Furthermore, we demonstrate that stage-specific NF-B activation, mediated by Nkx3.2, regulates chondrocyte viability during cartilage maturation.
- Department of Biochemistry, Yonsei University, SEOUL, 120-749, Republic of Korea.
- Department of Anatomy, Yonsei University College of Medicine, SEOUL, 120-752, Republic of Korea.
- These authors contributed equally to this work.
Correspondence to: Dae-Won Kim1 e-mail: kimdw@yonsei.ac.kr
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