title: SQSTM1 and Paget's disease of bone.
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.
authors.affiliation: School of Biomedical Sciences, University of Nottingham Medical School, Queen's Medical Centre, Nottingham NG7 2UH, UK. robert.layfield@nottingham.ac.uk
authors.forename: R
authors.initials: R
authors.lastname: Layfield
authors.forename: L J
authors.initials: LJ
authors.lastname: Hocking
mesh_terms: D004252:DNA Mutational Analysis; D006801:Humans; D008954:Models, Biological; D008958:Models, Molecular; D009154:Mutation; D010001:Osteitis Deformans / Q000235:genetics*; D017434:Protein Structure, Tertiary; D011506:Proteins / Q000737:chemistry / Q000378:metabolism; D025801:Ubiquitin / Q000737:chemistry
chemical_list: D011506:Proteins; D025801:Ubiquitin