|
Osteitis Deformans
|
0.100 |
Biomarker
|
disease |
BEFREE |
Our results indicate that p62 predominantly suppresses murine <i>in vitro</i> osteoclast differentiation and highlight previously undetected Paget's disease-like phenotypes in p62<sup>-/-</sup> mice <i>in vivo</i>.
|
29555685 |
2018 |
|
Osteitis Deformans
|
0.100 |
GeneticVariation
|
disease |
BEFREE |
Here we consider how knowledge of the impact of PDB-associated SQSTM1 mutations (several of which are now known to be relevant for ALS/FTLD) on these pathways, as well as the locations of the mutations within the p62 primary sequence, may provide new insights into ALS/FTLD disease mechanisms.
|
24486447 |
2014 |
|
Osteitis Deformans
|
0.100 |
GeneticVariation
|
disease |
BEFREE |
These mutations that are located in the ubiquitin-associated domain (UBA domain) of the p62 protein have already been described in Paget's disease and ALS patients carrying these mutations had both concomitant Paget's disease.
|
23417734 |
2013 |
|
Osteitis Deformans
|
0.100 |
GeneticVariation
|
disease |
BEFREE |
The condition has a strong genetic component, with mutations affecting the SQSTM1 gene that encodes the p62 protein often found in PDB patients, although environmental factors also play an important role in disease aetiology.
|
19858527 |
2010 |
|
Osteitis Deformans
|
0.100 |
AlteredExpression
|
disease |
BEFREE |
These findings clearly indicate that the overexpression of p62 in PDB patients induces important shifts in the pathways activated by RANKL and up-regulates osteoclast functions.
|
19589897 |
2009 |
|
Osteitis Deformans
|
0.100 |
GeneticVariation
|
disease |
BEFREE |
Further, mutations affecting the UBA domain (ubiquitin-associated domain) of p62 are commonly found in patients with the skeletal disorder PDB (Paget's disease of bone).
|
18481983 |
2008 |
|
Osteitis Deformans
|
0.100 |
GeneticVariation
|
disease |
BEFREE |
These results indicate that this PDB-associated p62 mutation is not sufficient to induce PDB and suggest that additional factors acting together with p62 mutation are necessary for the development of PDB in vivo.
|
18765443 |
2008 |
|
Osteitis Deformans
|
0.100 |
Biomarker
|
disease |
BEFREE |
Mutations affecting the receptor activator of NF-kappaB signaling axis can result in human skeletal disorders, including those identified in the C-terminal ubiquitin-associated (UBA) domain of p62 in patients with Paget disease of bone.
|
18083707 |
2008 |
|
Osteitis Deformans
|
0.100 |
GeneticVariation
|
disease |
BEFREE |
To further clarify the functional impact of p62 mutations associated with PDB, we assessed the effect of p62 mutation (a novel mutation: K378X, and previously reported mutations: P392L and E396X) on RANK-induced NF-kappaB activation and compared this with the effect of wildtype p62.
|
16813535 |
2006 |
|
Osteitis Deformans
|
0.100 |
GeneticVariation
|
disease |
BEFREE |
Functional analyses of PDB (Paget's disease of bone)-associated mutants of the p62 [also known as SQSTM1 (sequestosome 1)] signalling adaptor protein represent an interesting paradigm for understanding not only the disease mechanism in this skeletal disorder, but also the critical determinants of ubiquitin recognition by an ubiquitin-binding protein.
|
17052185 |
2006 |
|
Osteitis Deformans
|
0.100 |
GeneticVariation
|
disease |
BEFREE |
To further clarify the mechanisms by which these mutations predispose to PDB, we have extended these analyses to study the ubiquitin-binding properties of the PDB-causing mutations in the context of the full-length p62 protein.
|
15765181 |
2005 |
|
Osteitis Deformans
|
0.100 |
Biomarker
|
disease |
BEFREE |
Thus, phenotypically identical substitution and deletion mutations do not appear to predispose to PDB through a mechanism dependent on a common loss of ubiquitin chain binding by p62.
|
12857745 |
2003 |