PXD056791-1

PXD056791 is an original dataset announced via ProteomeXchange.

Title	Nuclear GTPSCS functions as a lactyl-CoA synthetase to promote histone lactylation
Description	Histone lysine lactylation is a physiologically and pathologically relevant epigenetic pathway that can be stimulated by the Warburg effect and 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 identification of GTPSCS as a lactyl-CoA synthetase in the nucleus 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 lactylation, but not histone succinylation. This process is dependent on not only a nuclear localization signal in the GTPSCS G1 subunit, but also acetylation at G2 subunit residue K73 which mediates the interaction with p300. GTPSCS-p300 collaboration synergistically regulates histone H3K18la, subsequently enhancing the expression of GDF15. This process promotes the proliferation and radioresistance of gliomas. The GTPSCS represents the inaugural enzyme that can catalyze lactyl-CoA synthesis for epigenetic histone lactylation and regulate oncogenic gene expression patterns in glioma.
HostingRepository	PRIDE
AnnounceDate	2024-12-02
AnnouncementXML	Submission_2024-12-02_08:41:24.881.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Ruilong Liu
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	succinylated residue; lactic acid
Instrument	Q Exactive HF

Revision	Datetime	Status	ChangeLog Entry
0	2024-10-14 14:56:43	ID requested
⏵ 1	2024-12-02 08:41:25	announced

Dataset with its publication pending

submitter keyword: tumorigenesis, lactylation, the Warburg effect, radioresistance, epigenetics,GDF15, histone marks, p300, succinyl-CoA synthetase, lactyl-CoA, metabolic reprogramming, lactyl-CoA synthetase

Yingming Zhao
contact affiliation	Ben May Department for Cancer Research, The University of Chicago, Chicago, IL, 60637, USA
contact email	yzhao2@bsd.uchicago.edu
lab head
Ruilong Liu
contact affiliation	University of Chicago
contact email	ruilongliu@uchicago.edu
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD056791
     1. Label: PRIDE project
     2. Name: Nuclear GTPSCS functions as a lactyl-CoA synthetase to promote histone lactylation