PXD056047

PXD056047 is an original dataset announced via ProteomeXchange.

Title	PDCD6 modulates LC3-associated phagocytosis-mediated antimicrobial defense by regulating lactate metabolism
Description	LC3-associated phagocytosis (LAP) is critical in host defense against invading pathogens, but the molecular mechanism for LAP activation is still unclear. Here, we find programmed cell death 6 (PDCD6) as a negative regulator of LAP. PDCD6 deficiency in mice and macrophages induces enhanced bactericidal activity and LAP formation. In parallel, lactate dehydrogenase A (LDHA) activity and lactate production is induced in macrophages challenged with bacteria, Zymosan or Pam3CSK4, while genetic ablation or pharmacological inhibition of LDHA reduces lactate levels and impairs bactericidal activity in vivo and in vitro. Mechanistically, PDCD6 interacts with LDHA to downregulate lactate metabolism, leading to reduced RUBCN lactylation at lysine33 (K33). By contrast, PDCD6-deficiency increases RUBCN lactylation, thereby promotes RUBCN interaction with VPS34, LAP formation, and protective responses. Our results thus suggest a PDCD6-LDHA-lactate-RUBCN axis of innate immunity regulation that may both contribute to protection from infectious diseases and serve as targets for therapeutic development.
HostingRepository	PRIDE
AnnounceDate	2024-10-18
AnnouncementXML	Submission_2024-10-18_02:34:16.407.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Sun Lulu
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	No PTMs are included in the dataset
Instrument	Q Exactive

Revision	Datetime	Status	ChangeLog Entry
0	2024-09-20 02:00:21	ID requested
⏵ 1	2024-10-18 02:34:16	announced

Dataset with its publication pending

submitter keyword: Lactate, LAP,PDCD6

Tianliang Li
contact affiliation	College of Life Sciences, Shandong Normal University
contact email	li.tianliang@outlook.com
lab head
Sun Lulu
contact affiliation	Shandong Normal University
contact email	1723783573@qq.com
dataset submitter

Dataset FTP location NOTE: Most web browsers have now discontinued native support for FTP access within the browser window. But you can usually install another FTP app (we recommend FileZilla) and configure your browser to launch the external application when you click on this FTP link. Or otherwise, launch an app that supports FTP (like FileZilla) and use this address: ftp://ftp.pride.ebi.ac.uk/pride/data/archive/2024/10/PXD056047

PRIDE project URI

• PRIDE
  1. PXD056047
     1. Label: PRIDE project
     2. Name: PDCD6 modulates LC3-associated phagocytosis-mediated antimicrobial defense by regulating lactate metabolism