PXD035465

PXD035465 is an original dataset announced via ProteomeXchange.

Title	Human HCC crotonylation LC-MS/MS
Description	Crotonylation, a crotonyl-CoA-based nonenzymatic protein translational modification, has effects on diverse biological processes such as spermatogenesis, tissue injury, inflammation, and neuropsychiatric diseases1-6. Crotonylation is also decreased in hepatocellular carcinomas (HCCs)7, but the mechanism remains unknown. Here, we described the role of glutaryl-CoA dehydrogenase (GCDH) on tumor suppression. GCDH depletion promoted hepatocellular carcinoma progression and metastasis in vitro and in vivo, whereas its overexpression reversed these processes. As GCDH converts glutaryl-CoA to crotonyl-CoA to increase crotonylation levels, we used lysine crotonylome analysis and identified the pentose phosphate pathway and glycolysis-related genes PGD, TKT and ALDOC as GCDH-induced crotonylated targets. Crotonyl-bound targets showed allosteric effects that controlled their enzymatic activities, leading to decreases in ribose 5-phosphate and lactate production. The GCDH overexpression-induced pentose phosphate pathway blockade also stimulated peroxidation, synergizing with cell senescence and death modulators to induce these effects in GCDHhigh cells. These cells induced infiltration of immune cells by a paracrine senescence-associated secretory cell phenotype (SASP) to induce the self-clearance process. Meanwhile, GCDHlow cells recruited enough programmed cell death protein 1 positive (PD1+) targeted T cells for anti-PD1 therapy. Consistently, GCDH levels correlated with HCC prognoses and anti-tumor immunity outcomes, resulting in a tumor suppressive or vulnerable anti-PD1 therapeutic microenvironment in liver cancer.
HostingRepository	iProX
AnnounceDate	2022-07-21
AnnouncementXML	Submission_2022-07-20_20:56:05.060.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Yuanxiang Lao
SpeciesList	scientific name: Homo sapiens; NCBI TaxID: 9606;
ModificationList	N6-crotonyl-L-lysine
Instrument	timsTOF Pro

Revision	Datetime	Status	ChangeLog Entry
0	2022-07-20 20:55:22	ID requested
⏵ 1	2022-07-20 20:56:05	announced

Dataset with its publication pending

submitter keyword: Human, Hepatocellular carcinoma, Crotonylation, LC-MS/MS

Beicheng Sun
contact affiliation	Nanjing University
contact email	sunbc@nju.edu.cn
lab head
Yuanxiang Lao
contact affiliation	Nanjing University
contact email	yx_lao@126.com
dataset submitter

iProX dataset URI