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

Overview

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.

publication date

  • February 1, 2004

Research

keywords

  • Bone Remodeling
  • Carrier Proteins
  • Glycoproteins
  • Immediate-Early Proteins
  • Osteogenesis
  • Protein Kinase C
  • Receptors, Cytoplasmic and Nuclear
  • Transcription Factors

Identity

Scopus Document Identifier

  • 0442325388

Digital Object Identifier (DOI)

  • 10.1016/s1534-5807(03)00403-9

PubMed ID

  • 14960283

Additional Document Info

volume

  • 6

issue

  • 2