PXD037672-1

PXD037672 is an original dataset announced via ProteomeXchange.

Title	Nuclear GTPSCS functions as a lactyl-CoA ligase to promote histone lactylation and glioma progression
Description	Histone lysine lactylation is a physiologically relevant epigenetic pathway that can be stimulated by the Warburg effect and hypoxia-associated L-lactate. Nevertheless, the mechanism by which cells use L-lactate to generate lactyl-CoA, the cofactor for the modification, and how this process is regulated remain unknown. Here, we report the identification of GTPSCS as a lactyl-CoA ligase using biochemistry and cell biology approaches. The mechanism of this catalytic activity was elucidated using the crystallographic structure of GTPSCS in complex with L-lactate, followed by mutagenesis experiments. GTPSCS translocates into the nucleus and interacts with p300 to form a functional lactyltransferase to elevate histone H3 lysine 18 lactylation (H3K18la). This process is dependent on not only a nuclear localization signal in the GTPSCS G1 subunit but also acetylation at the G2 subunit residue K73 (for the interaction between GTPSCS and p300). GTPSCS-p300-mediated histone H3K18la promotes glioma cell proliferation and tumor formation in mice. In addition, histone H3K18la is positively associated with glioma grade and poor prognosis in glioma patients. The LDHA-GTPSCS-lactyltransferase-histone Kla axis thus represents a signal-stimulated epigenetic pathway that mediates the downstream impact of the Warburg effect and hypoxia
HostingRepository	PRIDE
AnnounceDate	2024-12-04
AnnouncementXML	Submission_2024-12-04_01:17:10.414.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	He Huang
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	acetylated residue
Instrument	Q Exactive HF

Revision	Datetime	Status	ChangeLog Entry
0	2022-10-24 01:54:04	ID requested
⏵ 1	2024-12-04 01:17:10	announced

10.1016/J.CMET.2024.11.005;

submitter keyword: tumorigenesis, lactylation, the Warburg effect, histone marks, p300, hypoxia, Succinyl-CoA synthetase, lactyl-CoA ligase,epigenetics

He Huang
contact affiliation	Chinese Academy of Sciences Shanghai Institute of Materia Medica
contact email	hhuang@simm.ac.cn
lab head
He Huang
contact affiliation	Shanghai Institute of Materia Medica
contact email	hhuang.nu@gmail.com
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD037672
     1. Label: PRIDE project
     2. Name: Nuclear GTPSCS functions as a lactyl-CoA ligase to promote histone lactylation and glioma progression