Mutant p62/SQSTM1 UBA domains linked to Paget's disease of bone differ in their abilities to function as stabilization signals

Christian Heinen, Thomas P. Garner, Jed Long, Claudia Bottcher, Stuart H. Ralston, James R. Cavey, Mark S. Searle, Robert Layfield, Nico P. Dantuma

Research output: Contribution to journalArticlepeer-review


We show that the ubiquitin-associated domain (UBA) of human p62/sequestosome-1 (SQSTM1) can delay degradation of proteasome substrates in yeast. Taking advantage of naturally occurring mutant UBA domains that are linked to Paget's disease of bone (PDB), we found that three of the four mutant UBA domains tested in this study were able to inhibit proteasomal degradation, albeit not to the same extent as the wild-type domain. Interestingly, the stability measured as the fraction of folded protein, and not the ubiquitin binding properties, of the PDB-associated UBA domains correlated with their protective effects. These data suggest that the protective effect of UBA domains depends on their structural integrity rather than ubiquitin binding capabilities. (C) 2010 Federation of European Biochemical Societies. Published by Elsevier B.V. All rights reserved.

Original languageEnglish
Pages (from-to)1585-1590
Number of pages6
JournalFEBS Letters
Issue number8
Publication statusPublished - 16 Apr 2010

Cite this