PXD050147-1

PXD050147 is an original dataset announced via ProteomeXchange.

Title	SIRT1/SIRT3 are robust lysine delactylases and SIRT1-mediated delactylation regulates glycolysis
Description	Lysine lactylation (Kla), a newly identified epigenetic mark triggered by lactate during glycolysis, including the Warburg effect, marks a pivotal juncture between metabolic pathways and gene regulation. The discovery of enzymes such as p300 and HDAC1/3 has been pivotal in deciphering the regulatory dynamics of Kla, though questions about additional regulatory enzymes, their specific Kla substrates, and the underlying functional mechanisms persist. Our investigation bridges these knowledge gaps by identifying SIRT1 and SIRT3 as key "erasers" of Kla, providing insights into their selective regulatory impact on both histone and non-histone proteins. Through a quantitative proteomic analysis in wildtype, SIRT1 knockout, and SIRT3 knockout HepG2 cells, we delineated a comprehensive landscape of Kla and lysine acetylation (Kac) sites. The results demonstrate a distinct specificity in the substrates modified by SIRT1 and SIRT3, underscoring their differentiated roles in cellular signaling pathways. Particularly, we highlight the role of specific Kla modifications, such as those on the M2 splice isoform of pyruvate kinase (PKM2), in modulating metabolic pathways and cell proliferation, thereby expanding the recognized implications of Kla beyond its epigenetic roles. Therefore, this study paves the way for deeper understanding of the functional phenotypes and mechanisms of Kla, offering new insights into its broader biological significance.
HostingRepository	PRIDE
AnnounceDate	2025-05-06
AnnouncementXML	Submission_2025-05-06_13:12:22.824.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	2024-02-26 05:46:38	ID requested
⏵ 1	2025-05-06 13:12:23	announced

Du R, Gao Y, Yan C, Ren X, Qi S, Liu G, Guo X, Song X, Wang H, Rao J, Zang Y, Zheng M, Li J, Huang H, Sirtuin 1/sirtuin 3 are robust lysine delactylases and sirtuin 1-mediated delactylation regulates glycolysis. iScience, 27(10):110911(2024) [pubmed]

10.1016/j.isci.2024.110911;

submitter keyword: Lysine lactylation, Protein post-translational modifications, Delactylase, Proteomics, Sirtuins

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. PXD050147
     1. Label: PRIDE project
     2. Name: SIRT1/SIRT3 are robust lysine delactylases and SIRT1-mediated delactylation regulates glycolysis