PXD043003-1

PXD043003 is an original dataset announced via ProteomeXchange.

Title	The function of ER-phagy receptors is regulated through phosphorylation-dependent ubiquitination pathways.
Description	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.
HostingRepository	PRIDE
AnnounceDate	2023-11-16
AnnouncementXML	Submission_2023-11-16_07:18:38.433.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Pablo Sanz Martinez
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	phosphorylated residue
Instrument	Q Exactive HF

Revision	Datetime	Status	ChangeLog Entry
0	2023-06-15 01:48:00	ID requested
⏵ 1	2023-11-16 07:18:38	announced
2	2024-10-22 06:14:38	announced	2024-10-22: Updated project metadata.

Dataset with its publication pending

submitter keyword: CK2, ER homeostasis, lysosomal degradation, ER remodeling, ER fragmentation, CHEK1, ATR, selective autophagy, ATM, ubiquitination., stress response, FAM134B, FAM134C,endoplasmic reticulum, mTOR

Alexandra Stolz
contact affiliation	Group leader, ER quality control, Institute for biochemistry II, Frankfurt am Main
contact email	stolz@em.uni-frankfurt.de
lab head
Pablo Sanz Martinez
contact affiliation	PhD student
contact email	P.SanzMartinez@med.uni-frankfurt.de
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD043003
     1. Label: PRIDE project
     2. Name: The function of ER-phagy receptors is regulated through phosphorylation-dependent ubiquitination pathways.