PXD034835

PXD034835 is an original dataset announced via ProteomeXchange.

Title	Regulation of membrane fluidity by RNF145-triggered degradation of the lipid hydrolase ADIPOR2
Description	The regulation of membrane lipid composition is critical for cellular homeostasis. Cells are particularly sensitive to phospholipid saturation, with increased saturation causing membrane rigidification and lipotoxicity. How mammalian cells sense membrane lipid composition and reverse fatty acid (FA)-induced membrane rigidification is poorly understood. Here we systematically identify proteins that differ between mammalian cells fed saturated versus unsaturated FAs. The most differentially expressed proteins were two ER-resident polytopic membrane proteins: the E3 ubiquitin ligase RNF145 and the lipid hydrolase ADIPOR2. In unsaturated lipid membranes, RNF145 is stable, promoting its lipid-sensitive interaction, ubiquitination and degradation of ADIPOR2. When membranes become enriched in saturated FAs, RNF145 is rapidly auto-ubiquitinated and degraded, stabilising ADIPOR2, whose hydrolase activity restores lipid homeostasis and prevents lipotoxicity. We therefore identify RNF145 as a FA-responsive ubiquitin ligase which, together with ADIPOR2, define an autoregulatory pathway that controls cellular membrane lipid homeostasis and prevents acute lipotoxic stress.
HostingRepository	PRIDE
AnnounceDate	2023-11-14
AnnouncementXML	Submission_2023-11-14_08:57:33.823.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	James Williamson
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	monohydroxylated residue; iodoacetamide derivatized residue
Instrument	Orbitrap Fusion

Revision	Datetime	Status	ChangeLog Entry
0	2022-06-22 02:34:44	ID requested
1	2022-08-10 05:02:52	announced
⏵ 2	2023-11-14 08:57:34	announced	2023-11-14: Updated project metadata.

Dataset with its publication pending

submitter keyword: AP-MS, TMT,Oritrap Fusion

Paul Lehner
contact affiliation	Wellcome Trust Principal Research Fellow Honorary Consultant Infectious Diseases Cambridge Institute of Therapeutic Immunology and Infectious Disease Jeffrey Cheah Biomedical Centre Univeristy of Cambridge
contact email	pjl30@cam.ac.uk
lab head
James Williamson
contact affiliation	University of Cambridge
contact email	jcw76@cam.ac.uk
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD034835
     1. Label: PRIDE project
     2. Name: Regulation of membrane fluidity by RNF145-triggered degradation of the lipid hydrolase ADIPOR2