8 research outputs found
Low Dose Proteasome Inhibition Affects Alternative Splicing
Protein degradation by the ubiquitin proteasome system
ensures controlled degradation of structural proteins, signaling mediators,
and transcription factors. Inhibition of proteasome function by specific
proteasome inhibitors results in dose-dependent cellular effects ranging
from induction of apoptosis to protective stress responses. The present
study seeks to identify nuclear regulators mediating the protective
stress response to low dose proteasome inhibition. Primary human endothelial
cells were treated with low doses of the proteasome inhibitor MG132
for 2 h, and proteomic analysis of nuclear extracts was performed.
Using a 2-D differential in gel electrophoresis (DIGE) approach, we
identified more than 24 splice factors to be differentially regulated
by low dose proteasome inhibition. In particular, several isoforms
of hnRNPA1 were shown to be increased, pointing toward altered posttranslational
modification of hnRNPA1 upon proteasome inhibition. Elevated levels
of splice factors were associated with a different alternative splicing
pattern in response to proteasome inhibition as determined by Affymetrix
exon array profiling. Of note, we observed alternative RNA processing
for stress associated genes such as caspases and heat shock proteins.
Our study provides first evidence that low dose proteasome inhibition
affects posttranscriptional regulation of splice factors and early
alternative splicing events
Low Dose Proteasome Inhibition Affects Alternative Splicing
Protein degradation by the ubiquitin proteasome system
ensures controlled degradation of structural proteins, signaling mediators,
and transcription factors. Inhibition of proteasome function by specific
proteasome inhibitors results in dose-dependent cellular effects ranging
from induction of apoptosis to protective stress responses. The present
study seeks to identify nuclear regulators mediating the protective
stress response to low dose proteasome inhibition. Primary human endothelial
cells were treated with low doses of the proteasome inhibitor MG132
for 2 h, and proteomic analysis of nuclear extracts was performed.
Using a 2-D differential in gel electrophoresis (DIGE) approach, we
identified more than 24 splice factors to be differentially regulated
by low dose proteasome inhibition. In particular, several isoforms
of hnRNPA1 were shown to be increased, pointing toward altered posttranslational
modification of hnRNPA1 upon proteasome inhibition. Elevated levels
of splice factors were associated with a different alternative splicing
pattern in response to proteasome inhibition as determined by Affymetrix
exon array profiling. Of note, we observed alternative RNA processing
for stress associated genes such as caspases and heat shock proteins.
Our study provides first evidence that low dose proteasome inhibition
affects posttranscriptional regulation of splice factors and early
alternative splicing events
Role of the Putative Histidine Kinase BP1092 in Bordetella pertussis Virulence Regulation and Intracellular Survival
Bordetella pertussis persists
inside
host cells, and virulence factors are crucial for intracellular adaptation.
The regulation of B. pertussis virulence
factor transcription primarily occurs through the modulation of the
two-component system (TCS) known as BvgAS. However, additional regulatory
systems have emerged as potential contributors to virulence regulation.
Here, we investigate the impact of BP1092, a putative TCS histidine
kinase that shows increased levels after bacterial internalization
by macrophages, on B. pertussis proteome
adaptation under nonmodulating (Bvg+) and modulating (Bvg−)
conditions. Using mass spectrometry, we compare B.
pertussis wild-type (wt), a BP1092-deficient mutant
(ΔBP1092), and a ΔBP1092 trans-complemented strain under both conditions. We find an altered abundance
of 10 proteins, including five virulence factors. Specifically, under
nonmodulating conditions, the mutant strain showed decreased levels
of FhaB, FhaS, and Cya compared to the wt. Conversely, under modulating
conditions, the mutant strain exhibited reduced levels of BvgA and
BvgS compared to those of the wt. Functional assays further revealed
that the deletion of BP1092 gene impaired B. pertussis ability to survive within human macrophage THP-1 cells. Taken together,
our findings allow us to propose BP1092 as a novel player involved
in the intricate regulation of B. pertussis virulence factors and thus in adaptation to the intracellular environment.
The data have been deposited to the ProteomeXchange Consortium via
the PRIDE partner repository with the data set identifier PXD041940
Role of the Putative Histidine Kinase BP1092 in Bordetella pertussis Virulence Regulation and Intracellular Survival
Bordetella pertussis persists
inside
host cells, and virulence factors are crucial for intracellular adaptation.
The regulation of B. pertussis virulence
factor transcription primarily occurs through the modulation of the
two-component system (TCS) known as BvgAS. However, additional regulatory
systems have emerged as potential contributors to virulence regulation.
Here, we investigate the impact of BP1092, a putative TCS histidine
kinase that shows increased levels after bacterial internalization
by macrophages, on B. pertussis proteome
adaptation under nonmodulating (Bvg+) and modulating (Bvg−)
conditions. Using mass spectrometry, we compare B.
pertussis wild-type (wt), a BP1092-deficient mutant
(ΔBP1092), and a ΔBP1092 trans-complemented strain under both conditions. We find an altered abundance
of 10 proteins, including five virulence factors. Specifically, under
nonmodulating conditions, the mutant strain showed decreased levels
of FhaB, FhaS, and Cya compared to the wt. Conversely, under modulating
conditions, the mutant strain exhibited reduced levels of BvgA and
BvgS compared to those of the wt. Functional assays further revealed
that the deletion of BP1092 gene impaired B. pertussis ability to survive within human macrophage THP-1 cells. Taken together,
our findings allow us to propose BP1092 as a novel player involved
in the intricate regulation of B. pertussis virulence factors and thus in adaptation to the intracellular environment.
The data have been deposited to the ProteomeXchange Consortium via
the PRIDE partner repository with the data set identifier PXD041940
Role of the Putative Histidine Kinase BP1092 in Bordetella pertussis Virulence Regulation and Intracellular Survival
Bordetella pertussis persists
inside
host cells, and virulence factors are crucial for intracellular adaptation.
The regulation of B. pertussis virulence
factor transcription primarily occurs through the modulation of the
two-component system (TCS) known as BvgAS. However, additional regulatory
systems have emerged as potential contributors to virulence regulation.
Here, we investigate the impact of BP1092, a putative TCS histidine
kinase that shows increased levels after bacterial internalization
by macrophages, on B. pertussis proteome
adaptation under nonmodulating (Bvg+) and modulating (Bvg−)
conditions. Using mass spectrometry, we compare B.
pertussis wild-type (wt), a BP1092-deficient mutant
(ΔBP1092), and a ΔBP1092 trans-complemented strain under both conditions. We find an altered abundance
of 10 proteins, including five virulence factors. Specifically, under
nonmodulating conditions, the mutant strain showed decreased levels
of FhaB, FhaS, and Cya compared to the wt. Conversely, under modulating
conditions, the mutant strain exhibited reduced levels of BvgA and
BvgS compared to those of the wt. Functional assays further revealed
that the deletion of BP1092 gene impaired B. pertussis ability to survive within human macrophage THP-1 cells. Taken together,
our findings allow us to propose BP1092 as a novel player involved
in the intricate regulation of B. pertussis virulence factors and thus in adaptation to the intracellular environment.
The data have been deposited to the ProteomeXchange Consortium via
the PRIDE partner repository with the data set identifier PXD041940
Role of the Putative Histidine Kinase BP1092 in Bordetella pertussis Virulence Regulation and Intracellular Survival
Bordetella pertussis persists
inside
host cells, and virulence factors are crucial for intracellular adaptation.
The regulation of B. pertussis virulence
factor transcription primarily occurs through the modulation of the
two-component system (TCS) known as BvgAS. However, additional regulatory
systems have emerged as potential contributors to virulence regulation.
Here, we investigate the impact of BP1092, a putative TCS histidine
kinase that shows increased levels after bacterial internalization
by macrophages, on B. pertussis proteome
adaptation under nonmodulating (Bvg+) and modulating (Bvg−)
conditions. Using mass spectrometry, we compare B.
pertussis wild-type (wt), a BP1092-deficient mutant
(ΔBP1092), and a ΔBP1092 trans-complemented strain under both conditions. We find an altered abundance
of 10 proteins, including five virulence factors. Specifically, under
nonmodulating conditions, the mutant strain showed decreased levels
of FhaB, FhaS, and Cya compared to the wt. Conversely, under modulating
conditions, the mutant strain exhibited reduced levels of BvgA and
BvgS compared to those of the wt. Functional assays further revealed
that the deletion of BP1092 gene impaired B. pertussis ability to survive within human macrophage THP-1 cells. Taken together,
our findings allow us to propose BP1092 as a novel player involved
in the intricate regulation of B. pertussis virulence factors and thus in adaptation to the intracellular environment.
The data have been deposited to the ProteomeXchange Consortium via
the PRIDE partner repository with the data set identifier PXD041940
Role of the Putative Histidine Kinase BP1092 in Bordetella pertussis Virulence Regulation and Intracellular Survival
Bordetella pertussis persists
inside
host cells, and virulence factors are crucial for intracellular adaptation.
The regulation of B. pertussis virulence
factor transcription primarily occurs through the modulation of the
two-component system (TCS) known as BvgAS. However, additional regulatory
systems have emerged as potential contributors to virulence regulation.
Here, we investigate the impact of BP1092, a putative TCS histidine
kinase that shows increased levels after bacterial internalization
by macrophages, on B. pertussis proteome
adaptation under nonmodulating (Bvg+) and modulating (Bvg−)
conditions. Using mass spectrometry, we compare B.
pertussis wild-type (wt), a BP1092-deficient mutant
(ΔBP1092), and a ΔBP1092 trans-complemented strain under both conditions. We find an altered abundance
of 10 proteins, including five virulence factors. Specifically, under
nonmodulating conditions, the mutant strain showed decreased levels
of FhaB, FhaS, and Cya compared to the wt. Conversely, under modulating
conditions, the mutant strain exhibited reduced levels of BvgA and
BvgS compared to those of the wt. Functional assays further revealed
that the deletion of BP1092 gene impaired B. pertussis ability to survive within human macrophage THP-1 cells. Taken together,
our findings allow us to propose BP1092 as a novel player involved
in the intricate regulation of B. pertussis virulence factors and thus in adaptation to the intracellular environment.
The data have been deposited to the ProteomeXchange Consortium via
the PRIDE partner repository with the data set identifier PXD041940