Golgi stress-induced transcriptional changes mediated by MAPK signaling and three ETS transcription factors regulate MCL1 splicing.
| Title: | Golgi stress-induced transcriptional changes mediated by MAPK signaling and three ETS transcription factors regulate MCL1 splicing. |
|---|---|
| Authors: | Baumann J; BioMed X Innovation Center, 69120 Heidelberg, Germany.; Ignashkova TI; BioMed X Innovation Center, 69120 Heidelberg, Germany.; Chirasani SR; BioMed X Innovation Center, 69120 Heidelberg, Germany.; Ramírez-Peinado S; BioMed X Innovation Center, 69120 Heidelberg, Germany.; Alborzinia H; BioMed X Innovation Center, 69120 Heidelberg, Germany.; Gendarme M; BioMed X Innovation Center, 69120 Heidelberg, Germany.; Kuhnigk K; BioMed X Innovation Center, 69120 Heidelberg, Germany.; Kramer V; BioMed X Innovation Center, 69120 Heidelberg, Germany.; Lindemann RK; Translational Innovation Platform Oncology, Merck Biopharma, Merck KGaA, 64293 Darmstadt, Germany.; Reiling JH; BioMed X Innovation Center, 69120 Heidelberg, Germany reiling@bio.mx. |
| Source: | Molecular biology of the cell [Mol Biol Cell] 2018 Jan 01; Vol. 29 (1), pp. 42-52. Date of Electronic Publication: 2017 Nov 08. |
| Publication Type: | Journal Article |
| Language: | English |
| Journal Info: | Publisher: American Society for Cell Biology Country of Publication: United States NLM ID: 9201390 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1939-4586 (Electronic) Linking ISSN: 10591524 NLM ISO Abbreviation: Mol Biol Cell Subsets: MEDLINE |
| Imprint Name(s): | Original Publication: Bethesda, MD : American Society for Cell Biology, c1992- |
| MeSH Terms: | MAP Kinase Signaling System*/drug effects ; Stress, Physiological*/drug effects ; Transcription, Genetic*/drug effects; Alternative Splicing/*genetics ; Golgi Apparatus/*metabolism ; Myeloid Cell Leukemia Sequence 1 Protein/*genetics ; Proto-Oncogene Proteins c-ets/*metabolism; Alternative Splicing/drug effects ; Apoptosis/drug effects ; Brefeldin A/pharmacology ; Cytoprotection/drug effects ; Golgi Apparatus/drug effects ; Mitogen-Activated Protein Kinases/metabolism ; Monensin/pharmacology ; Pyridines/pharmacology ; Quinolines/pharmacology ; Small Molecule Libraries/pharmacology ; Spliceosomes/drug effects ; Spliceosomes/metabolism ; Transcriptome/drug effects ; Transcriptome/genetics ; Up-Regulation/drug effects ; A549 Cells ; Gene Expression Profiling ; Gene Knockdown Techniques ; HEK293 Cells ; HeLa Cells ; Humans |
| Abstract: | The secretory pathway is a major determinant of cellular homoeostasis. While research into secretory stress signaling has so far mostly focused on the endoplasmic reticulum (ER), emerging data suggest that the Golgi itself serves as an important signaling hub capable of initiating stress responses. To systematically identify novel Golgi stress mediators, we performed a transcriptomic analysis of cells exposed to three different pharmacological compounds known to elicit Golgi fragmentation: brefeldin A, golgicide A, and monensin. Subsequent gene-set enrichment analysis revealed a significant contribution of the ETS family transcription factors ELK1, GABPA/B, and ETS1 to the control of gene expression following compound treatment. Induction of Golgi stress leads to a late activation of the ETS upstream kinases MEK1/2 and ERK1/2, resulting in enhanced ETS factor activity and the transcription of ETS family target genes related to spliceosome function and cell death induction via alternate MCL1 splicing. Further genetic analyses using loss-of-function and gain-of-function experiments suggest that these transcription factors operate in parallel.; (© 2018 Baumann et al. This article is distributed by The American Society for Cell Biology under license from the author(s). Two months after publication it is available to the public under an Attribution–Noncommercial–Share Alike 3.0 Unported Creative Commons License (http://creativecommons.org/licenses/by-nc-sa/3.0).) |
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| Substance Nomenclature: | 0 (Myeloid Cell Leukemia Sequence 1 Protein); 0 (Proto-Oncogene Proteins c-ets); 0 (Pyridines); 0 (Quinolines); 0 (Small Molecule Libraries); 0 (golgicide A); 20350-15-6 (Brefeldin A); 906O0YJ6ZP (Monensin); EC 2.7.11.24 (Mitogen-Activated Protein Kinases) |
| Entry Date(s): | Date Created: 20171110 Date Completed: 20181224 Latest Revision: 20240606 |
| Update Code: | 20260130 |
| PubMed Central ID: | PMC5746065 |
| DOI: | 10.1091/mbc.E17-06-0418 |
| PMID: | 29118074 |
| Database: | MEDLINE |
Journal Article