PXD051557-1

PXD051557 is an original dataset announced via ProteomeXchange.

Title	Proximity Labeling and Genetic Screening Reveals the Role of DSG2/Siglec-9 Axis in Suppressing Macrophage Phagocytosis
Description	In current study, we have established a combined strategy using proximity labeling and genetic screening to identify the cellular ligands of Siglec-9. Our use of proximity labeling using APEX2 fusion proteins followed by quantitative proteomics allowed us to efficiently label and enrich cell surface protein ligands that directly interact with Siglec-9 via sialic acid moieties. By combining with CRISPR knockout screening, we were able to identify functionally significant ligands. We confirmed at the cellular level that DSG2 expressed on cell surfaces directly interacts with Siglec-9, and this interaction is mediated by site-specific N-glycans on the ECD of DGS2. We also demonstrated the binding between DSG2 on A375 melanoma cells and Siglec-9 on macrophages contributes significantly to Siglec-9 signaling and blocking the DSG2-Siglec-9 axis by either DSG2 knockdown or anti-Siglec-9 antibody, releases immune-suppression and increases phagocytosis. Our findings revealed an important ligand in cancer cells for the immunosuppressive receptor Siglec-9, and suggest the potential of disrupting DSG2-Siglec-9 signaling axis in anti-cancer therapy.
HostingRepository	PRIDE
AnnounceDate	2024-12-23
AnnouncementXML	Submission_2024-12-23_02:42:25.688.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	wu ying
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	monohydroxylated residue; iodoacetamide derivatized residue
Instrument	Q Exactive

Revision	Datetime	Status	ChangeLog Entry
0	2024-04-18 05:51:15	ID requested
⏵ 1	2024-12-23 02:42:26	announced

Dataset with its publication pending

submitter keyword: Siglec-9, APEX2, DSG2, proximity label

Mao Yang
contact affiliation	Sun Yat-sen University
contact email	maoyang3@mail.sysu.edu.cn
lab head
wu ying
contact affiliation	School of Pharmaceutical Sciences, Sun Yat-sen University, Guangzhou, China
contact email	wuying56@mail2.sysu.edu.cn
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD051557
     1. Label: PRIDE project
     2. Name: Proximity Labeling and Genetic Screening Reveals the Role of DSG2/Siglec-9 Axis in Suppressing Macrophage Phagocytosis