Consequently, the peripheral cysteine mutants retained cytoprotective activity, whereas the PD-associated mutant [M26I]DJ-1 failed to suppress ASK1 activity and nuclear export of the death domain-associated protein Daxx and did not promote cytoprotection.
These findings suggest that ER stress-induced ASK1-p38 activation, which is triggered by the accumulation of Ins(C96Y), plays an important role in the pathogenesis of diabetes.
These findings suggest that ER stress-induced ASK1-p38 activation, which is triggered by the accumulation of Ins(C96Y), plays an important role in the pathogenesis of diabetes.
A human genome-wide association study identified that <i>AIP1</i> (<i>ASK1-interacting protein-1</i>; also identified as <i>DAB2IP</i>) gene variants confer susceptibility to cardiovascular disease, but the underlying mechanism is unknown.
In order to assess the importance of this pathway in HD pathology, JNK inhibitors including dominant-negative mutants of upstream kinases (ASK1(K709R), MEKK1(D1369A)), a c-Jun mutant (Delta169c-Jun) and the active domain of the scaffold protein JIP-1/IBI (IBI-JBD) were tested for their ability to mitigate the effect of htt171-82Q.
Three new proteins; Receptor-interacting protein 1 (RIP1), Apoptosis signal-regulating kinase 1 (ASK1) and B-cell lymphoma 2 (Bcl-2) from Apoptosis Signaling Pathway revealed best CDOCKER energy with triclosan which was -26.88, -23.34 and -22.96 kcal/mol respectively.
Rearrangements were detected within 1p and 2q in MOTN-1 affecting expression of FGR, ZEB2, and CASP8, and within 6q in MOTN-1 and one T-LGL patient affecting MAP3K5 and IFNGR1.
In other contexts, both the NFκB (nuclear factor κB) pathway and the ASK1 (apoptosis signaling kinase 1) pathway have been shown to be regulated by both Grx1 and Trx1, and both pathways have been implicated in cell death signaling in model systems of PD.
In other contexts, both the NFκB (nuclear factor κB) pathway and the ASK1 (apoptosis signaling kinase 1) pathway have been shown to be regulated by both Grx1 and Trx1, and both pathways have been implicated in cell death signaling in model systems of PD.
Thioredoxin and binding proteins (ASK1 and TBP2) appear to control apoptosis or metabolic states such as carbohydrate and lipid metabolism related to diseases such as diabetes and atherosclerosis.
The position of the mutations and the loss of heterozygosity of MAP3K5 and MAP3K9 in 85% and 67% of melanoma samples, respectively, together suggest that the mutations are likely to be inactivating.