Bone Abstracts

see PP493....

Abstract: Paget’s disease of bone (PDB) is characterised by focal lesions of local bone turnover driven by overactive osteoclasts, which often contain nuclear and cytoplasmic inclusion bodies. Mutations affecting the sequestosome-1 (SQSTM1) ubiquitin-associated (UBA) domain have been identified in individuals with PDB. SQSTM1, also known as p62, is a ubiquitously-expressed scaffold protein of 62 kDa that functions in multiple signalling pathways important for cell surviva...

Paget’s disease of Bone (PDB) is caused by mutations in the gene encoding Sequestosome-1 (Q17STM1 or p62) that affect the C-terminal Ubiquitin-Associated (UBA) domain. A second isoform of Q17STM1 exists (referred to hereafter as 55kDa-Q17STM1), which lacks the N-terminal Phox and Bem1 (PB1) domain and has previously been reported to be ~45x more abundant than Q17STM1/p62 in osteoclasts. Mutations in the UBA domain will also occur in this isoform. Several of the UBA mutati...