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          Institute: MPI für experimentelle Endokrinologie     Collection: Arbeitsgruppe Leitges     Display Documents

ID: 214456.0, MPI für experimentelle Endokrinologie / Arbeitsgruppe Leitges
The atypical PKC-interacting protein p62 is an important mediator of RANK-activated osteoclastogenesis
Authors:Duran, A.; Serrano, M.; Leitges, M.; Flores, J. M.; Picard, S.; Brown, J. P.; Moscat, J.; Diaz-Meco, M. T.
Date of Publication (YYYY-MM-DD):2004-02
Title of Journal:Dev Cell
Issue / Number:2
Start Page:303
End Page:309
Review Status:Peer-review
Audience:Experts Only
Abstract / Description: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.
Free Keywords:Animals
; Blotting, Southern
; Bone Marrow
; Bone Remodeling/*physiology
; Bone Resorption
; Carrier Proteins/genetics/*metabolism
; Cell Count
; Cells, Cultured
; Comparative Study
; Electrophoretic Mobility Shift Assay
; Embryo
; Enzyme-Linked Immunosorbent 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
External Publication Status:published
Document Type:Article
Affiliations:MPI für experimentelle Endokrinologie
Identifiers:URL: [ID No:1]
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