The atypical PKC-interacting protein p62 is an important mediator of RANK-activated osteoclastogenesis.
Journal:
Dev. Cell 2004 FebAuthors:
Durán A, Serrano M, Leitges M, Flores JM, Picard S, Brown JP, Moscat J, Diaz-Meco MT
Abstract
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,
...[more] 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.[less]
Mesh Headings:
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