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 Böttcher, Stuart H. Ralston, James R. Cavey, Mark S. Searle, Robert Layfield, Nico P. Dantuma

Research output: Contribution to journalArticle

11 Citations (Scopus)

Abstract

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.

Original languageEnglish (US)
Pages (from-to)1585-1590
Number of pages6
JournalFEBS Letters
Volume584
Issue number8
DOIs
StatePublished - Apr 2010
Externally publishedYes

Fingerprint

Osteitis Deformans
Ubiquitin
Bone
Stabilization
Degradation
Structural integrity
Proteasome Endopeptidase Complex
Yeast
Yeasts
Substrates

Keywords

  • Paget's disease of bone
  • Proteasome
  • Rad23
  • Sequestosome-1
  • Stabilization signal
  • Ubiquitin
  • Ubiquitin binding domain

ASJC Scopus subject areas

  • Biochemistry
  • Biophysics
  • Cell Biology
  • Genetics
  • Molecular Biology
  • Structural Biology

Cite this

Mutant p62/SQSTM1 UBA domains linked to Paget's disease of bone differ in their abilities to function as stabilization signals. / Heinen, Christian; Garner, Thomas P.; Long, Jed; Böttcher, Claudia; Ralston, Stuart H.; Cavey, James R.; Searle, Mark S.; Layfield, Robert; Dantuma, Nico P.

In: FEBS Letters, Vol. 584, No. 8, 04.2010, p. 1585-1590.

Research output: Contribution to journalArticle

Heinen, C, Garner, TP, Long, J, Böttcher, C, Ralston, SH, Cavey, JR, Searle, MS, Layfield, R & Dantuma, NP 2010, 'Mutant p62/SQSTM1 UBA domains linked to Paget's disease of bone differ in their abilities to function as stabilization signals', FEBS Letters, vol. 584, no. 8, pp. 1585-1590. https://doi.org/10.1016/j.febslet.2010.03.018
Heinen, Christian ; Garner, Thomas P. ; Long, Jed ; Böttcher, Claudia ; Ralston, Stuart H. ; Cavey, James R. ; Searle, Mark S. ; Layfield, Robert ; Dantuma, Nico P. / Mutant p62/SQSTM1 UBA domains linked to Paget's disease of bone differ in their abilities to function as stabilization signals. In: FEBS Letters. 2010 ; Vol. 584, No. 8. pp. 1585-1590.
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AU - Ralston, Stuart H.

AU - Cavey, James R.

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