PXD056693

PXD056693 is an original dataset announced via ProteomeXchange.

Title	FGF21 regulates ER-stress and the Unfolded Protein Response through Sulfide Signaling
Description	Fibroblast growth factor 21 (FGF21) is an endocrine hormone with broad metabolic actions at supraphysiological concentrations, but unclear physiological function, with recent data suggesting a link to endoplasmic reticulum (ER)-stress. ER-stress activates the unfolded protein response (UPR), a cellular repair mechanism maintaining cellular homeostasis during protein folding stress. Using APEX2 proximity labelling, we assessed the intracellular action of FGF21 at its receptor β-klotho (KLB), and discovered associations to protein folding in the ER, ER-stress, and H2S production. We found that FGF21 enhances the UPR, and that this action is blunted by either genetic or pharmacological inhibition of sulfide signaling, and phenocopied by an H2S-donor in vivo . Strikingly, we found that even physiological levels of FGF21 KLB-dependently modulate the UPR via increased hepatic H2S production. Our data hence identify a novel physiological role of FGF21 and further indicate that sulfide signaling is a core second messenger of the UPR.
HostingRepository	PRIDE
AnnounceDate	2026-06-16
AnnouncementXML	Submission_2026-06-16_12:02:47.654.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Stefanie Hauck
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: NEWT:9606;
ModificationList	deamidated residue; iodoacetamide derivatized residue
Instrument	Q Exactive HF

Revision	Datetime	Status	ChangeLog Entry
0	2024-10-10 05:59:55	ID requested
⏵ 1	2026-06-16 12:02:48	announced

10.1016/J.CMET.2026.05.011;

submitter keyword: APEX2, ER-stress,FGF21

Prof. Dr. Timo Müller
contact affiliation	Helmholtz Munich, Institute for Diabetes and Obesity, Ingolstädter Landstraße 1 · D-85764 Neuherberg
contact email	timodirk.mueller@helmholtz-munich.de
lab head
Stefanie Hauck
contact affiliation	Research Unit Protein Science, Helmholtz Zentrum München
contact email	hauck@helmholtz-muenchen.de
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD056693
     1. Label: PRIDE project
     2. Name: FGF21 regulates ER-stress and the Unfolded Protein Response through Sulfide Signaling