• Publications
  • Influence
Reversible inhibitor of p97, DBeQ, impairs both ubiquitin-dependent and autophagic protein clearance pathways
TLDR
N2,N4-Dibenzylquinazoline-2,4-diamine (DBeQ) was identified as a selective, potent, reversible, and ATP-competitive p97 inhibitor that blocks multiple processes that have been shown by RNAi to depend on p97, including degradation of ubiquitin fusion degradation and endoplasmic reticulum-associated degradation pathway reporters.
Guidelines for the use and interpretation of assays for monitoring autophagy (3rd edition)
TLDR
There continues to be confusion regarding acceptable methods to measure autophagy, especially in multicellular eukaryotes, so it is important to update guidelines for monitoring autophagic activity in different organisms.
Targeted sequencing and identification of genetic variants in sporadic inclusion body myositis
TLDR
Genetic evaluation in sIBM may be clinically meaningful and lend insight into its pathomechanism, and in vitro analysis of two VCP variants found that they both disrupted autophagy similar to other pathogenic mutations.
Specific inhibition of p97/VCP ATPase and kinetic analysis demonstrate interaction between D1 and D2 ATPase domains.
TLDR
Four p97 inhibitors have differential responses to Walker A and B mutations, to disease-causing IBMPFD mutations, and to the presence of the N domain binding cofactor protein p47, providing the first evidence that p97 cofactors and disease mutations can alter p97 inhibitor potency.
Keap1/Cullin3 Modulates p62/SQSTM1 Activity via UBA Domain Ubiquitination.
TLDR
It is found that Keap1/Cullin3 ubiquitinates p62 at lysine 420 within its UBA domain, suggesting that the ubiquitination of p62's UBAdomain at l Lysine 420 may regulate p62' function and be disrupted in p62-associated disease.
Altered cofactor regulation with disease-associated p97/VCP mutations
TLDR
The results show that cofactors play a critical role in controlling p97 ATPase activity, and suggest that lack of cofactor-regulated communication may contribute to p97-associated disease pathogenesis.
p97 Disease Mutations Modulate Nucleotide-Induced Conformation to Alter Protein–Protein Interactions
TLDR
It is proposed that p97/adaptor PPIs are coupled to p97 conformational states and nucleotides and the adaptor proteins p37 and p47 bind 8-fold more weakly to the ADP-bound conformation of wild-type p97 and MSP1 mutants.
A novel mutation in VCP causes Charcot-Marie-Tooth Type 2 disease.
TLDR
Functional studies showed that the Glu185Lys variant impaired autophagic function leading to the accumulation of immature autophagosomes, and should be considered for genetically undefined Charcot-Marie-Tooth disease type 2.
Structure–Activity Relationship Study Reveals ML240 and ML241 as Potent and Selective Inhibitors of p97 ATPase
TLDR
The results nominate ML240 as a promising starting point for the development of a novel agent for the chemotherapy of cancer, and provide a rationale for developing pathway‐specific p97 inhibitors.
Lysyl-tRNA Synthetase-generated Lysyl-Adenylate Is a Substrate for Histidine Triad Nucleotide Binding Proteins*
  • T. Chou, C. Wagner
  • Medicine, Biology
    Journal of Biological Chemistry
  • 16 February 2007
TLDR
It is demonstrated that the lysyl-AMP intermediate formed by LysRS is a natural substrate for Hints and suggests a potential highly conserved regulatory role for Hint on LysRS and possibly other aminoacyl-tRNA synthetases.
...
1
2
3
4
5
...