Low Dose Proteasome Inhibition
Affects Alternative Splicing
Sven Bieler
Elke Hammer
Manuela Gesell-Salazar
Uwe VoĢlker
Karl Stangl
Silke Meiners
10.1021/pr300435c.s002
https://acs.figshare.com/articles/journal_contribution/Low_Dose_Proteasome_Inhibition_Affects_Alternative_Splicing/2500054
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.
2016-02-20 15:46:49
Low Dose Proteasome Inhibition Affects
alternative RNA processing
ubiquitin proteasome system
dose proteasome inhibition
DIGE
proteasome inhibitor MG 132
hnRNPA 1
heat shock proteins
24 splice factors
proteasome inhibition
proteasome inhibitors results
Affymetrix exon array
splice factors