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Calcified Tissue International

, Volume 75, Issue 5, pp 347–357 | Cite as

SQSTM1 and Paget’s Disease of Bone

  • R. Layfield
  • L. J. Hocking
Article

Abstract

Mutations in the Sequestosome 1 gene (SQSTM1; also known as p62) have recently been identified as the cause of 5q35-linked Paget’s disease of bone (PDB). All of the mutations identified to date affect the ubiquitin-associated (UBA) domain of SQSTM1, a region of the protein that binds noncovalently to ubiquitin. In this review we consider the possible functional significance of the SQSTM1-ubiquitin interaction, and consequences of the SQSTM1 UBA domain mutations. Clarification of the in vivo roles of SQSTM1 in bone-cell function will be central to improving our understanding of the molecular pathogenesis of PDB and related conditions.

Keywords

SQSTM1 p62 Paget’s disease of bone Ubiquitin UBA domain 

Notes

Acknowledgments

We wish to acknowledge support of the Wellcome Trust (R.L.) and the Arthritis Research Campaign (L.J.H.). We thank J. Cavey and H. Majed for helpful comments on the manuscript, and M. Searle and B. Ciani for assistance in the preparation of Figure 5.

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Copyright information

© Springer-Verlag 2004

Authors and Affiliations

  1. 1.School of Biomedical SciencesUniversity of Nottingham Medical School, Queen’s Medical CentreNottinghamUK
  2. 2.University of Aberdeen Medical SchoolInstitute of Medical SciencesForesterhillScotland, UK

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