Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Pivot Concepts:
Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Target Concepts:
Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Query: EC:2.3.1.177 (
BIS
)
957
document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)
B-cell lymphoma (BCL)-2-interacting cell death suppressor (
BIS
) has diverse cellular functions depending on its binding partners. However, little is known about the effects of biochemical modification of
BIS
on its various activities under oxidative stress conditions. In this study, we showed that H
2
O
2
reduced
BIS
mobility on SDS-polyacrylamide gels in a time-dependent manner via the activation of extracellular signaling-regulated kinase (ERK). The combined results of mass spectroscopy and computational prediction identified Thr285 and Ser289 in
BIS
as candidate residues for phosphorylation by ERK under oxidative stress conditions. Deletion of these sites resulted in a partial reduction in the H
2
O
2
-induced mobility shift relative to that of the wild-type
BIS
protein; overexpression of the deletion mutant sensitized A172 cells to H
2
O
2
-induced cell death without increasing the level of intracellular reactive oxygen species. Expression of the
BIS
deletion mutant decreased the level of
heat shock protein
(
HSP
) 70 mRNA following H
2
O
2
treatment, which was accompanied by impaired nuclear translocation of heat shock transcription factor (HSF) 1. Co-immunoprecipitation assays revealed that the binding of wild-type
BIS
to HSF1 was decreased by oxidative stress, while the binding of the
BIS
deletion mutant to HSF1 was not affected. These results indicate that ERK-dependent phosphorylation of
BIS
has a role in the regulation of nuclear translocation of HSF1 likely through modulation of its interaction affinity with HSF1, which affects HSP70 expression and sensitivity to oxidative stress.
...
PMID:ERK-mediated phosphorylation of BIS regulates nuclear translocation of HSF1 under oxidative stress. 2765 16
