PXD070146-1

PXD070146 is an original dataset announced via ProteomeXchange.

Title	Starvation-induced Hsc70 O-GlcNAcylation activates chaperone-mediated autophagy
Description	O-linked β-N-acetylglucosamine (O-GlcNAc) functions as a nutrition rheostat to mediate cellular signaling pathways. It fluctuates in response to various nutritional factors, for instance, glucose. Previous investigations have shown that both glucose surplus and glucose deprivation upregulate O-GlcNAcylation levels. Meanwhile, starvation also activates autophagy, including chaperone-mediated autophagy (CMA). In the CMA pathway, heat shock cognate 70 kDa protein (HSC70) recognizes client proteins that bear a KFERQ pentapeptide motif, and delivers them to lysosome associated membrane protein type 2A (Lamp2a) on the lysosome, allowing lysosomal degradation of client proteins. Herein we show that Hsc70 interacts with O-GlcNAc transferase (OGT) and is O-GlcNAcylation, both of which are elevated when glucose is depleted. We further validated that Hsc70 O-GlcNAcylation occurs at T430, according to a previous chemoproteomic screen. T430 sits at the hydrophobic pocket of Hsc70. Moreover, we used label-free quantitative mass spectrometry to analyze HSC70-WT and HSC70-T430A interactome, identified a new CMA substrate, Ataxin-10, and mapped a potential KFERQ motif on Ataxin-10. In sum, our work suggests that CMA and O-GlcNAcylation intersect at HSC70, the CMA chaperone. HSC70 O-GlcNAcylation is essential to alter its client profile in response to nutrient availability.
HostingRepository	PRIDE
AnnounceDate	2026-06-29
AnnouncementXML	Submission_2026-06-28_16:24:08.042.xml
DigitalObjectIdentifier	https://doi.org/10.6019/PXD070146
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Supported dataset by repository
PrimarySubmitter	Wen Zhou
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: NEWT:9606;
ModificationList	No PTMs are included in the dataset
Instrument	Orbitrap Fusion Lumos

Revision	Datetime	Status	ChangeLog Entry
0	2025-10-31 02:26:39	ID requested
⏵ 1	2026-06-28 16:24:08	announced

10.1016/j.jbc.2026.113165;

Xu N, Wang X, Zhang J, Zhao J, Yan S, Zhou W, Chi W, Li J, Starvation-induced HSC70 O-GlcNAcylation activates chaperone-mediated autophagy. J Biol Chem, 302(7):113165(2026) [pubmed]

10.6019/PXD070146;

submitter keyword: Hsc70

O-GlcNAc

Chaperone-mediated autophagy

Ataxin-10

OGT

Wen Zhou
contact affiliation	Peking University
contact email	wen.zhou@pku.edu.cn
lab head
Wen Zhou
contact affiliation	Peking University
contact email	wen.zhou@pku.edu.cn
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD070146
     1. Label: PRIDE project
     2. Name: Starvation-induced Hsc70 O-GlcNAcylation activates chaperone-mediated autophagy