We have studied the effects of various PDB-causing mutations of SQSTMl on the in vitro ubiquitin-binding properties of the p62 protein. All mutations caused loss of monoubiquitin-binding and impaired K48-linked polyubiquitin-binding, which was only evident at physiological temperature. This suggests that SQSTMI mutations predispose to PDB through a common mechanism that depends on loss of ubiquitin-binding by p62.
- Paget's disease of bone
- ubiquitin-associated domain
- familial expansile osteolysis
- interacting protein P62
- UBA domain