PXD051568

PXD051568 is an original dataset announced via ProteomeXchange.

Title	Opportunistic pathogen Porphyromonas gingivalis targets the LC3B-ceramide complex and mediates lethal mitophagy resistance in oral tumors
Description	Mechanisms by which Porphyromonas gingivalis (P. gingivalis) infection enhances oral tumor growth or resistance to cell death remain elusive. Here, we determined that P. gingivalis infection mediates therapeutic resistance via inhibiting lethal mitophagy in cancer cells and tumors. Mechanistically, P. gingivalis targets the LC3B-ceramide complex by associating with LC3B via bacterial major fimbriae (FimA) protein, preventing ceramide-dependent mitophagy in response to various therapeutic agents. Moreover, ceramide-mediated mitophagy is induced by Annexin A2 (ANXA2)-ceramide association, involving the E142 residue of ANXA2. Inhibition of ANXA2-ceramide-LC3B complex formation by wild-type P. gingivalis prevented ceramide-dependent mitophagy. Moreover, a FimA-deletion mutant P. gingivalis variant had no inhibitory effects on ceramide-dependent mitophagy. Further, 16S rRNA sequencing of oral tumors indicated that P. gingivalis infection altered the microbiome of the tumor macroenvironment in response to ceramide analog treatment in mice. Thus, these data provide a mechanism describing the pro-survival roles of P. gingivalis in oral tumors.
HostingRepository	PRIDE
AnnounceDate	2024-10-22
AnnouncementXML	Submission_2024-10-22_06:46:49.833.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Jennifer Bethard
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606; scientific name: Porphyromonas gingivalis; NCBI TaxID: 837;
ModificationList	No PTMs are included in the dataset
Instrument	Orbitrap Fusion Lumos

Revision	Datetime	Status	ChangeLog Entry
0	2024-04-18 13:34:48	ID requested
1	2024-06-23 01:26:32	announced
⏵ 2	2024-10-22 06:46:50	announced	2024-10-22: Updated project metadata.

10.1016/j.isci.2024.109860;

Sheridan M, Chowdhury N, Wellslager B, Oleinik N, Kassir MF, Lee HG, Engevik M, Peterson Y, Pandruvada S, Szulc ZM, Yilmaz Ö, Ogretmen B, targets the LC3B-ceramide complex and mediates lethal mitophagy resistance in oral tumors. iScience, 27(6):109860(2024) [pubmed]

submitter keyword: Therapeutic resistance, Oral Cancers,Ceramide

Ceramide-dependent mitophagy

Sphingolipid metabolism

Oral infection

Oral microbiota

Besim Ogretmen
contact affiliation	Medical University of South Carolina Department of Biochemistry and Molecular Biology,Hollings Cancer Center
contact email	ogremten@musc.edu
lab head
Jennifer Bethard
contact affiliation	Medical University of SC
contact email	bethard@musc.edu
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/2024/06/PXD051568

PRIDE project URI

• PRIDE
  1. PXD051568
     1. Label: PRIDE project
     2. Name: Opportunistic pathogen Porphyromonas gingivalis targets the LC3B-ceramide complex and mediates lethal mitophagy resistance in oral tumors