Proteomics

Dataset Information

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The function of ER-phagy receptors is regulated through phosphorylation-dependent ubiquitination pathways.


ABSTRACT: Selective autophagy of the endoplasmic reticulum (ER), known as ER-phagy, is an important regulator of ER remodeling and is critical to maintaining cellular homeostasis during environmental changes. We recently showed that members of the FAM134 family play a role during stress-induced ER-phagy. However, the mechanisms on how they are activated remain largely unknown. In this study, we analyzed mTOR-mediated phosphorylation of FAM134 as a trigger of FAM134-driven ER-phagy. An unbiased screen of kinase inhibitors revealed that CK2 is essential for ER-phagy driven by FAM134B and FAM134C after inhibition of mTOR. Using superresolution microscopy, we showed that CK2 activity is essential for the formation of high-density groups of FAM134B and FAM134C. Continually, the FAM134B and FAM134C proteins that carry point mutations of selected serine residues within their reticulon homology domain are unable to form high-density clusters. Furthermore, we provide evidence that ubiquitination regulates ER-phagy receptors and that dense clustering of FAM134B and FAM134C requires events upstream of ubiquitination. Treatment with the CK2 inhibitor SGC-CK2-1 or mutation of phosphosites prevents Torin1-induced ER-phagy flux as well as ubiquitination of FAM134 proteins, and consistently treatment with E1 inhibitor suppresses Torin1-induced ER-phagy flux. Therefore, we propose that CK2 dependent phosphorylation of ER-phagy receptors precedes ubiquitin-dependent activation of ER-phagy flux.

INSTRUMENT(S): Q Exactive HF

ORGANISM(S): Homo Sapiens (human)

TISSUE(S): Epithelial Cell

DISEASE(S): Osteosarcoma

SUBMITTER: Pablo Sanz Martinez  

LAB HEAD: Alexandra Stolz

PROVIDER: PXD043003 | Pride | 2023-11-16

REPOSITORIES: Pride

Dataset's files

Source:
Action DRS
20220311_MAA_PS_FAMB_DMSO_1.raw Raw
20220311_MAA_PS_FAMB_DMSO_2.raw Raw
20220311_MAA_PS_FAMB_DMSO_3.raw Raw
20220311_MAA_PS_FAMB_DMSO_4.raw Raw
20220311_MAA_PS_FAMB_TORIN_1.raw Raw
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