EDF1 binds collided ribosomes and facilitates recruitment of translational repressors GIGYF2/EIF4E2 and initiates JUN-mediated transcriptional response
Ontology highlight
ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE149565 | GEO | 2020/08/02
REPOSITORIES: GEO
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Project description:EDF1 binds collided ribosomes and facilitates recruitment of translational repressors GIGYF2/EIF4E2 and initiates JUN-mediated transcriptional response
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Project description:To further dissect whether and how activated JUN reconfigures the chromatin landscape, we performed Chromatin Immunoprecipitation (ChIP)-seq analyses for H3K4me1 and H3K27ac. Based on the significant increase of H3K27ac levels at H3K4me1+ sites, we identified 3,017 JUN-activated enhancers in JUN WT cells. In contrast, JUN AA fails to significantly induce H3K27ac accumulation at these regions. Their enrichment levels at JUN-activated enhancers were significantly decreased after JNKi treatment. Besides, these enhancers are directly driven by JUN, especially phosphorylated JUN.
2022-12-09 | GSE196345 | GEO
Project description:To examine the effects of phosphorylated JUN-mediated enhancers activation on gene expression, we conducted RNA-seq analysis in JUN wildtype (WT) or JUN inactive mutant (JUN AA) overexpressed MRC5 cells. The expression levels of genes associated with JUN-activated enhancers are significantly upregulated in JUN WT cells rather than in JUN AA cells. To quantify the effects of JUN inactivation on gene expression, we also performed RNA-seq analysis in JNKi-treated induced CAFs (iCAFs). We observed that JNKi significantly reduced expression levels of JUN-activated enhancers-associated genes.
2022-12-09 | GSE196351 | GEO
Project description:To determine target genes, biological functions of Jun and mechanisms of gene regulation by Jun in regenerating neurons, gene expression profiling was carried out of axotomized and uninjured facial motor neurons in floxed c-Jun mice crossed with nestin-cre mice. Nestin-promoter-driven Cre ensures deletion of Jun in the central nervous system including facial motor neurons. KO animals were Jun Flox/Fox Cre+, while WT animals were Jun Flox/Flox, Cre-.
2021-11-17 | GSE162977 | GEO
Project description:This SuperSeries is composed of the following subset Series: GSE39928: Murine livers post DEN treatment: c-Jun f/f vs. c-Jun Dli [35MM] GSE39929: Murine livers post DEN treatment: c-Jun f/f vs. c-Jun Dli [40MM] GSE39930: Murine livers post DEN treatment: c-Jun f/f vs. c-Jun Dli [41MM] GSE39931: Murine livers post DEN treatment: c-Jun f/f vs. c-Jun Dli [43MM] Refer to individual Series ** Six samples in each Series represent the same set of biological source material hybridized to 4 different arrays (named IMP internal: 35MM, 40MM, 41MM, and 43MM).
2012-08-07 | E-GEOD-39932 | biostudies-arrayexpress
Project description:Interventions: Control:FOLFOX or CAPEOX chemtherapy;Experimental group 1:Si-Jun-Zi decoction;Experimental group 2:enteral nutrition combine with Chemotherapy;Experimental group 3:Si-Jun-Zi decoction + enteral nutrition
Primary outcome(s): Intestinal barrier function
Study Design: Parallel
| 2689141 | ecrin-mdr-crc
Project description:Elevated c-Jun levels result in apoptosis and are evident in neurodegenerative disorders such as Alzheimer's disease and dementia and after global cerebral insults such as stroke and epilepsy. NMDA receptor (NMDAR) antagonists block c-Jun upregulation and prevent neuronal cell death following excitotoxic insults. However, little is known about the molecular mechanisms that regulate c-Jun abundance in neurons. Here we show that PRR7, a component of synaptic junctions, can upregulate c-Jun levels by inhibiting its ubiquitination in neurons. PRR7 interacts with the GLUN1 subunit of NMDARs and is upregulated in the nucleus following NMDAR activation. We show that PRR7 interacts with the E3 ligase SCFFBW7 (FBW7) and blocks the FBW7-mediated ubiquitination of c-Jun. PRR7 overexpression increases c-Jun-dependent transcriptional activity and promotes neuronal death. Microarray assays indicate that both Prr7 knockdown or overexpression alter the abundance of c-Jun-regulated transcripts associated with cellular viability as well as synaptic function. Moreover, Prr7 knockdown attenuates NMDA-mediated excitotoxicity in primary neuronal cultures. Our results show that PRR7 links NMDAR activity to c-Jun function and provide insight into the processes that underlie NMDA-dependent excitotoxicity. Four biological replicas of each of the four conditions: NO = not transduced with virus; NT = transduced with control lentiviruses containing a non-targeting shRNA sequence; KD = transduced with lentiviruses expressing PRR7-specific shRNAs; OE= transduced with lentiviruses to overexpress PRR7.
2014-10-25 | E-GEOD-62686 | biostudies-arrayexpress
Project description:Elevated c-Jun levels result in apoptosis and are evident in neurodegenerative disorders such as Alzheimer's disease and dementia and after global cerebral insults such as stroke and epilepsy. NMDA receptor (NMDAR) antagonists block c-Jun upregulation and prevent neuronal cell death following excitotoxic insults. However, little is known about the molecular mechanisms that regulate c-Jun abundance in neurons. Here we show that PRR7, a component of synaptic junctions, can upregulate c-Jun levels by inhibiting its ubiquitination in neurons. PRR7 interacts with the GLUN1 subunit of NMDARs and is upregulated in the nucleus following NMDAR activation. We show that PRR7 interacts with the E3 ligase SCFFBW7 (FBW7) and blocks the FBW7-mediated ubiquitination of c-Jun. PRR7 overexpression increases c-Jun-dependent transcriptional activity and promotes neuronal death. Microarray assays indicate that both Prr7 knockdown or overexpression alter the abundance of c-Jun-regulated transcripts associated with cellular viability as well as synaptic function. Moreover, Prr7 knockdown attenuates NMDA-mediated excitotoxicity in primary neuronal cultures. Our results show that PRR7 links NMDAR activity to c-Jun function and provide insight into the processes that underlie NMDA-dependent excitotoxicity.
2014-10-25 | GSE62686 | GEO
Project description:Serine/threonine kinase 40 (Stk40) was previously identified as a direct target gene of pluripotency-associated transcription factor Oct4 and its overexpression could facilitate differentiation of mouse embryonic stem cells (mESCs) towards the extraembryonic endoderm. Stk40-/- mice are lethal at the perinatal stage, displaying multiple organ failures. However, the molecular mechanisms underlying the physiological functions of Stk40 remain elusive. Here, we report that Stk40 ablation compromises the mesoderm differentiation from mESCs in vitro and in embryos. Mechanistically, Stk40 interacts with both mammalian constitutive photomorphogenic protein 1 (Cop1) and c-Jun, promoting degradation of c-Jun. Consequently, Stk40 knockout leads to c-Jun protein accumulation, which, in turn, might suppress the Wnt signaling activity and impair the mesoderm differentiation process. Overall, this study reveals that Stk40, together with Cop1, represent a novel axis for modulating c-Jun protein levels within an appropriate range during mesoderm differentiation from mESCs. Our finding provides new insight into the molecular mechanism regulating c-Jun protein stability and may have potential for managing related cellular disorders.
2019-05-14 | PXD012579 | Pride
Project description:Problems arising during translation of mRNAs lead to ribosome stalling and collisions with trailing ribosomes. These collisions are known to trigger a series of events including degradation of the stalled nascent polypeptide, decay of the problematic mRNAs, and ribosome rescue. However, the systemic cellular response of ribosome collision has not been explored. Here, we uncover a novel function for ribosome collisions in signal transduction. Using multiple translation elongation inhibitors and cellular stress conditions, we show that ribosome collisions activate both the SAPK (Stress Activated Protein Kinase) and GCN2-mediated cellular stress response pathways that lead to apoptosis and the integrated stress response (ISR), respectively. We further show that the MAPKKK ZAK functions as the sentinel for ribosome collisions, and ZAK is required for activation of both SAPKs p38/JNK and GCN2 signaling pathways. Selective ribosome profiling and biochemistry demonstrate that ZAK preferentially associates with the minimal unit of colliding ribosomes, the disome, inducing ZAK phosphorylation. While ZAK associates with elongating ribosomes under non-stressed conditions, activation of ZAK is specifically trigger by colliding ribosomes. Together, these results provide new insights into how perturbation of translational homeostasis, as read-out by colliding ribosomes, regulates cell fate.
2020-08-18 | GSE141459 | GEO