| Autor: |
Vanzyl, Erin J., Blackmore, Alex B., Sayed, Hadil, Rick, Kayleigh R.C., Fernando, Pasan, McKay, Bruce C. |
| Jazyk: |
angličtina |
| Rok vydání: |
2019 |
| DOI: |
10.1101/821363 |
| Popis: |
The spliceosome assembles on pre-mRNA in a stepwise manner through five successive pre-spliceosome complexes. The spliceosome functions to remove introns from pre-mRNAs to generate mature mRNAs that encode functional proteins. Many small molecule inhibitors of the spliceosome have been identified and they are cytotoxic. However, little is known about the mechanisms leading to cell death. Activating transcription factor 3 (ATF3) is a transcription factor that can stimulate apoptotic cell death in response to a variety of cellular stresses. Here, ATF3 protein levels increased in cultured human and mouse cells in response to cytotoxic levels of the two splicing inhibitors tested: pladienolide B (PB) and isoginkgetin (IGG), that target different pre-spliceosome complexes. Importantly, deletion of ATF3 protected mouse embryonic fibroblasts to these splicing inhibitors. Our results indicate that both splicing inhibitors activate ATF3, and that ATF3 is contributing to the sensitivity of MEFs to these compounds. |
| Databáze: |
OpenAIRE |
| Externí odkaz: |
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