Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
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Gene/Protein
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Target Concepts:
Gene/Protein
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Query: UMLS:C0079731 (
B-cell lymphoma
)
16,671
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
Heat shock factor 1 (HSF1), a transcription factor activated by various stressors, regulates proliferation and apoptosis by inducing expression of target genes, such as heat shock proteins and Bcl-2 (
B-cell lymphoma
2) interacting cell death suppressor (
BIS
). HSF1 also directly interacts with
BIS
, although it is still unclear whether this interaction is critical in the regulation of glioblastoma stem cells (GSCs). In this study, we examined whether small interfering RNA-mediated
BIS
knockdown decreased protein levels of HSF1 and subsequent nuclear localization under GSC-like sphere (SP)-forming conditions. Consistent with
BIS
depletion, HSF1 knockdown also reduced sex determining region Y (SRY)-box 2 (SOX2) expression, a marker of stemness, accompanying the decrease in SP-forming ability and matrix metalloprotease 2 (MMP2) activity. When HSF1 or
BIS
knockdown was combined with temozolomide (TMZ) treatment, a standard drug used in glioblastoma therapy, apoptosis increased, as measured by an increase in poly (ADP-ribose) polymerase (PARP) cleavage, whereas cancer stem-like properties, such as colony-forming activity and SOX2 protein expression, decreased. Taken together, our findings suggest that targeting
BIS
or HSF1 could be a viable therapeutic strategy for GSCs resistant to conventional TMZ treatment.
...
PMID:Heat Shock Factor 1 Depletion Sensitizes A172 Glioblastoma Cells to Temozolomide via Suppression of Cancer Stem Cell-Like Properties. 2824 25
