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Updated: Jun 15, 2025

Study of Protein-protein Interactions in Autophagy Research
Published on: September 9, 2017
Function of CSNK2/CK2 selectively affects the endoplasmic reticulum and the Golgi apparatus in mtor-mediated
Pablo Sanz-Martinez1,2, Rayene Berkane1,2, Alexandra Stolz1,2
1Institute of Biochemistry 2 (IBC2), Goethe University, Frankfurt am Main, Germany.
Abstract:
Selective macroautophagy/autophagy of the endoplasmic reticulum, known as reticulophagy/ER-phagy, is essential to maintain ER homeostasis. We recently showed that members of the autophagy receptor family RETREG/FAM134 are regulated by phosphorylation-dependent ubiquitination. In an unbiased screen we had identified several kinases downstream of MTOR with profound impact on reticulophagy flux, including ATR and CSNK2/CK2. Inhibition of CSNK2 by SGC-CK2-1 prevented regulatory ubiquitination of RETREG1/FAM134B and RETREG3/FAM134C upon autophagy activation as well as the formation of high-density RETREG1- and RETREG3-clusters. Here we report on additional resource data of global proteomics upon CSNK2 and ATR inhibition, respectively. Our data suggests that the function of CSNK2 is mainly limited to the ER/reticulophagy and Golgi/Golgiphagy, while ATR inhibition by VE-822 affects the vast majority of organelles/selective autophagy pathways.Abbreviation: ATRi: ATR inhibitor VE-822; CSNK2i: CSNK2 inhibitor SGC-CK2-1; ER: endoplasmic reticulum.
Insights
Selective autophagy, or ER-phagy, maintains endoplasmic reticulum (ER) homeostasis. CSNK2 inhibition impacts ER-phagy, while ATR inhibition affects multiple organelle autophagy pathways.
Area of Science:
- Cell Biology
- Molecular Biology
- Autophagy Research
Background:
- Selective autophagy, including reticulophagy/ER-phagy, is crucial for endoplasmic reticulum (ER) homeostasis.
- Autophagy receptors like RETREG/FAM134 are regulated by phosphorylation-dependent ubiquitination.
- Kinases downstream of MTOR, such as ATR and CSNK2/CK2, influence reticulophagy flux.
Purpose of the Study:
- To investigate the global proteomics changes upon inhibition of CSNK2 and ATR.
- To elucidate the specific roles of CSNK2 and ATR in selective autophagy pathways.
Main Methods:
- Global proteomics analysis.
- Inhibition of CSNK2 using SGC-CK2-1.
- Inhibition of ATR using VE-822.
- Analysis of regulatory ubiquitination and receptor clustering.
Main Results:
- CSNK2 inhibition prevented regulatory ubiquitination of RETREG1 and RETREG3, and formation of RETREG clusters.
- CSNK2 inhibition's effects were primarily limited to ER/reticulophagy and Golgi/Golgiphagy.
- ATR inhibition (ATRi) broadly impacted most organelle/selective autophagy pathways.
Conclusions:
- CSNK2 plays a specific role in ER/reticulophagy and Golgi/Golgiphagy regulation.
- ATR has a more widespread role, affecting the majority of selective autophagy pathways.
- These findings provide resource data for understanding kinase regulation of selective autophagy.
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