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

Duran, A., Serrano, M., Leitges, M., Flores, J. M., Picard, S., Brown, J. P., et al. (2004). The atypical PKC-interacting protein p62 is an important mediator of RANK-activated osteoclastogenesis. Developmental Cell, 6(2), 303-309. Retrieved from http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=14960283.

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Item Permalink: http://hdl.handle.net/11858/00-001M-0000-0012-EE62-6 Version Permalink: http://hdl.handle.net/11858/00-001M-0000-0028-95EC-B
Genre: Journal Article

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 Creators:
Duran, A., Author
Serrano, M., Author
Leitges, M.1, Author              
Flores, J. M., Author
Picard, S., Author
Brown, J. P., Author
Moscat, J., Author
Diaz-Meco, M. T., Author
Affiliations:
1Department of Genes and Behavior, MPI for biophysical chemistry, Max Planck Society, ou_persistent34              

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Free keywords: Animals; Blotting, Southern; Bone Marrow; Bone Remodeling/physiology; Bone Resorption; Carrier Proteins/genetics/*metabolism; Cell Count; Cells, Cultured; Comparative Study; ElectrophoreticMobility Shift Assay; Embryo; Enzyme-Linked mmunosorbent Assay; Fibroblasts/drug effects/metabolism; Gene Expression/physiology; Glycoproteins/genetics/physiology; Hematoxylin/metabolism; Immediate-Early Proteins/genetics/metabolism; Immunoblotting; Interleukin-6/blood; Macrophage Colony-Stimulating Factor/pharmacology; Macrophages/metabolism; Mice; Mice, Knockout; NF-kappa B/metabolism; Osteoclasts/metabolism; Osteogenesis/physiology; Parathyroid Hormone-Related; Protein/metabolism; Precipitin Tests; Protein Kinase C/genetics/metabolism; Protein-Serine-Threonine Kinases/metabolism; Proteins/metabolism; Receptors, Cytoplasmic and Nuclear/genetics/physiology; Research Support, Non-U.S. Gov't; TNF Receptor-Associated Factor 6; Time Factors; Transcription Factors
 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, 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.

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Language(s): eng - English
 Dates: 2004-02
 Publication Status: Published in print
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 Rev. Method: Peer
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Title: Developmental Cell
Source Genre: Journal
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Pages: - Volume / Issue: 6 (2) Sequence Number: - Start / End Page: 303 - 309 Identifier: -