Dataset Information

Starvation-induced Hsc70 O-GlcNAcylation activates chaperone-mediated autophagy

ABSTRACT: 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.

INSTRUMENT(S):

ORGANISM(S): Homo Sapiens (human)

SUBMITTER: Wen Zhou

LAB HEAD: Wen Zhou

PROVIDER: PXD070146 | Pride | 2026-06-29

REPOSITORIES: Pride

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Dataset's files

Source:

			Action	DRS
	23-237_LJ0815_HA-HSC70-0.raw	Raw
	23-237_LJ0815_HA-HSC70-40A.raw	Raw
	23-237_LJ0815_HA-HSC70-Quantitation.mzML	Mzml
	23-237_LJ0815_HA-HSC70-Quantitation.mzid	Mzid
	23-237_LJ0815_HA-HSC70-T430A.raw	Raw

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Publications

Starvation-induced HSC70 O-GlcNAcylation activates chaperone-mediated autophagy.

Xu Ningda N Wang Xiangpeng X Zhang Jiyue J Zhao Jianxin J Yan Sheng S Zhou Wen W Chi Wei W Li Jing J

The Journal of biological chemistry 20260515 7

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 availability. Previous investigations have shown that glucose deprivation upregulates O-GlcNAcylation levels. Meanwhile, starvation also activates autophagy, in particular, chaperone-mediated autophagy (CMA). But it is unknown what signal activates CMA during starvation. In the CMA pathway, heat shock c ...[more]

PMID: 42142583

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