Over 50% cancer bears TP53 mutation, the highly stabilized mutant p53 protein drives tumorigenesis and progression. Mutation of not only cause loss-of-function dominant-negative effects (DNE), but also results in abnormal stability by regulation ubiquitin-proteasome system molecular chaperones that promote through gain-of-function effects. The accumulation is mainly regulated chaperones, includ...

Rheumatoid arthritis (RA) is a chronic, systemic inflammatory disease which affects approximately 1% of the population worldwide. Recent research on the role of heat shock proteins (Hsps) in RA development indicates that they may have pro- or anti-inflammatory effect, most probably via modulating cytokine secretion. We investigated type Th1 (INFγ, TNFα, IL-2) and type Th2 (IL-10, IL-6, IL-4) cy...

Ubiquitin accumulation in amyloid plaques is a pathological marker observed in the vast majority of neurodegenerative diseases, yet ubiquitin function in these inclusions is controversial. It has been suggested that ubiquitylated proteins are directed to inclusion bodies under stress conditions, when both chaperone-mediated refolding and proteasomal degradation are compromised or overwhelmed. A...

The structural mechanism by which Hsp70-type chaperones interact with Hsp40-type co-chaperones has been of great interest, yet still remains a matter of debate. Here, we used solution NMR spectroscopy to investigate the ATP-/ADP-dependent interactions between Escherichia coli HscA and HscB, the specialized Hsp70/Hsp40 molecular chaperones that mediate iron-sulfur cluster transfer. We observed t...

Prp43p catalyzes essential steps in pre-mRNA splicing and rRNA biogenesis. In splicing, Spp382p stimulates the Prp43p helicase to dissociate the postcatalytic spliceosome and, in some way, to maintain the integrity of the spliceosome assembly. Here we present a dosage interference assay to identify Spp382p-interacting factors by screening for genes that when overexpressed specifically inhibit t...

Parkinson disease (PD) is characterized by dopaminergic neurodegeneration and intracellular inclusions of alpha-synuclein amyloid fibers, which are stable and difficult to dissolve. Whether inclusions are neuroprotective or pathological remains controversial, because prefibrillar oligomers may be more toxic than amyloid inclusions. Thus, whether therapies should target inclusions, preamyloid ol...

AIMS Heat shock proteins (HSPs), known to inhibit apoptosis and promote cellular survival, are overexpressed in many tumours. We analysed the expression of relevant HSPs and heat shock factor 1 (HSF1) in classical Hodgkin lymphoma (cHL) and their relationship with caspase signalling pathways and patient outcome. METHODS AND RESULTS Using tissue microarrays (TMAs), most cases showed strong imm...

The DnaJ (Hsp40) cochaperone regulates the DnaK (Hsp70) chaperone by accelerating ATP hydrolysis in a cycle closely linked to substrate binding and release. The J-domain, the signature motif of the Hsp40 family, orchestrates interaction with the DnaK ATPase domain. We studied the J-domain by creating 42 mutant E. coli DnaJ variants and examining their phenotypes in various separate in vivo assa...