PXD056772-1

PXD056772 is an original dataset announced via ProteomeXchange.

Title	O-GlcNAcase SUMOylation studies identify the SUMO-code in chaperone-mediated autophagy
Description	O-GlcNAcase (OGA) is the sole eraser for the intracellular O-linked N-acetylglucosamine (O-GlcNAc). OGA has many roles in diverse processes, such as cancer and embryonic stem cells, but its exact regulating mechanism is far from understood. Herein we studied small ubiquitin-like modifier (SUMO) modification of OGA, and found that OGA is SUMOylated at K358. SUMOylation targets OGA to the chaperone-mediated autophagy (CMA) pathway, which shunts client proteins to the lysosome for degradation. We demonstrate that SUMOylation increases the association between OGA and Heat shock cognate protein (HSC70), the CMA chaperone, and facilitates its further degradation. We further mapped a SUMO-interacting motif (SIM) (VLIFD, aa. 195-199) on HSC70. Surprisingly, HSC70-SIM is essential for affinity with other CMA clients, such as PKM2. We thus posit that the SIM of HSC70 binds SUMOylated clients in a lock-and-key fashion to confer substrate selectivity during CMA. To validate our hypothesis, we used label-free quantitative mass spectrometry to study the HSC70-SIM mutant interactome, and generated a proteome-wide SUMO-mediated CMA client pool. We then validated our model by studying YEATS domain containing 2 (YEATS2) from the protein pool, and demonstrated that YEATS2 is SUMOylated at K592, which also targets YEATS2 to CMA. Our work unveils the SUMO-SIM interaction as a fundamental mechanism that governs CMA substrate selectivity and identifies a potential CMA client proteome to deepen our understanding of its pathophysiological relevance.
HostingRepository	iProX
AnnounceDate	2024-10-13
AnnouncementXML	Submission_2024-10-13_23:18:47.489.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Guangcan Shao
SpeciesList	scientific name: Homo sapiens; NCBI TaxID: 9606;
ModificationList	sumoylated lysine
Instrument	Q Exactive HF

Revision	Datetime	Status	ChangeLog Entry
0	2024-10-13 23:17:57	ID requested
⏵ 1	2024-10-13 23:18:47	announced

Dataset with its publication pending

submitter keyword: O-GlcNAcase, SUMOylation

Jing Li
contact affiliation	National Institute of Biological Sciences (Beijing)
contact email	jing_li@mail.cnu.edu.cn
lab head
Guangcan Shao
contact affiliation	National Institute of Biological Sciences (Beijing)
contact email	shaoguangcan@nibs.ac.cn
dataset submitter

iProX dataset URI