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The atypical PKC-interacting protein p62 is an important mediator of RANK-activated osteoclastogenesis.

Developmental cell | Feb 12, 2004

The atypical PKCs (aPKCs) have been implicated genetically in at least two independent signaling cascades that control NF-kappa B and cell polarity, through the interaction with the adapters p62 and Par-6, respectively. P62 binds TRAF6, which plays an essential role in osteoclastogenesis and bone remodeling. Recently, p62 mutations have been shown to be the cause of the 5q35-linked Paget's disease of bone, a genetic disorder characterized by aberrant osteoclastic activity. Here we show that p62, like TRAF6, is upregulated during RANK-L-induced osteoclastogenesis and that the genetic inactivation of p62 in mice leads to impaired osteoclastogenesis in vitro and in vivo, as well as inhibition of IKK activation and NF-kappa B nuclear translocation. In addition, RANK-L stimulation leads to the inducible formation of a ternary complex involving TRAF6, p62, and the aPKCs. These observations demonstrate that p62 is an important mediator during osteoclastogenesis and induced bone remodeling.

Pubmed ID: 14960283 RIS Download

Mesh terms: Animals | Blotting, Southern | Bone Marrow | Bone Remodeling | Bone Resorption | Carrier Proteins | Cell Count | Cells, Cultured | Electrophoretic Mobility Shift Assay | Embryo, Mammalian | Enzyme-Linked Immunosorbent Assay | Fibroblasts | Gene Expression | Glycoproteins | Hematoxylin | I-kappa B Kinase | Immediate-Early Proteins | Immunoblotting | Interleukin-6 | Macrophage Colony-Stimulating Factor | Macrophages | Mice | Mice, Knockout | NF-kappa B | Osteoclasts | Osteogenesis | Osteoprotegerin | Parathyroid Hormone-Related Protein | Precipitin Tests | Protein Kinase C | Protein Kinase C-epsilon | Protein-Serine-Threonine Kinases | Proteins | Receptors, Cytoplasmic and Nuclear | Receptors, Tumor Necrosis Factor | TNF Receptor-Associated Factor 6 | Time Factors | Transcription Factors

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