Molecular Biology of the Cell
Molecular Biology of the Cell
4 years ago

Golgi stress-induced transcriptional changes mediated by MAPK signaling and three ETS transcription factors regulate MCL1 splicing.

Hamed Alborzinia, Mathieu Gendarme, Sridhar R Chirasani, Kyra Kuhnigk, Jan Baumann, Valentin Kramer, Silvia Ramírez-Peinado, Tatiana I Ignashkova, Jan H Reiling, Ralph K Lindemann
The secretory pathway is a major determinant of cellular homoeostasis. While research into secretory stress signaling has so far mostly focused on the ER, emerging data suggests 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 (BFA), golgicide A (GCA) and monensin (MON). 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- as well as gain-of-function experiments suggest that these transcription factors operate in parallel.

Publisher URL: http://doi.org/10.1091/mbc.E17-06-0418

DOI: 10.1091/mbc.E17-06-0418

You might also like
Discover & Discuss Important Research

Keeping up-to-date with research can feel impossible, with papers being published faster than you'll ever be able to read them. That's where Researcher comes in: we're simplifying discovery and making important discussions happen. With over 19,000 sources, including peer-reviewed journals, preprints, blogs, universities, podcasts and Live events across 10 research areas, you'll never miss what's important to you. It's like social media, but better. Oh, and we should mention - it's free.

  • Download from Google Play
  • Download from App Store
  • Download from AppInChina

Researcher displays publicly available abstracts and doesn’t host any full article content. If the content is open access, we will direct clicks from the abstracts to the publisher website and display the PDF copy on our platform. Clicks to view the full text will be directed to the publisher website, where only users with subscriptions or access through their institution are able to view the full article.