PXD035002

PXD035002 is an original dataset announced via ProteomeXchange.

Title	Identification of potential substrates of TRABID in HeLa cells using SILAC
Description	Immune checkpoint blockades (ICBs) have been approved for treating multiple cancer types, but the response rate is limited for many solid tumors. Much efforts have been devoted to understand the mechanisms governing ICB therapy efficacy and the abundance of tumor-infiltrating lymphocytes is among the factors that influence on ICB responsiveness. The deubiquitinase TRABID was identified in our previous study as a positive regulator of autophagy by stabilizing VPS34, the class III PI3K critical for autophagosome formation. In this study, we identify an upregulation of TRABID in mitosis and its critical role in mitotic progression through deubiquitination and stabilization of AURKB and BIRC5, two subunits of the chromosome passenger complex governing multiple mitotic steps. Furthermore, TRABID depletion induces micronuclei phenotype, which is likely mediated by the combinatory defects in mitosis and autophagy. Consequently, TRABID depletion or inhibition activates cGAS/STING pathway to induce type I interferon production and inflammatory responses. TRABID depletion in tumors cells reduces tumor burden and promotes anti-tumor immune surveillance by increasing tumor infiltration of CD4+ and CD8+ T cells and NK cells and reducing Treg cells. Clinically, TRABID expression in multiple cancer types correlates negatively with the infiltration of anti-tumor immune cells and positively with that of pro-tumor immune cells. Our study supports a suppressive role of tumor-intrinsic TRABID in anti-tumor immunity and suggests TRABID inhibitor as a promising agent for enhancing the sensitivity of solid tumors to ICB therapy.
HostingRepository	PRIDE
AnnounceDate	2023-05-11
AnnouncementXML	Submission_2023-05-10_19:16:32.334.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	CHENHAN-HSIUN
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	isotope labeled residue
Instrument	LTQ Orbitrap

Revision	Datetime	Status	ChangeLog Entry
0	2022-06-30 03:16:10	ID requested
⏵ 1	2023-05-10 19:16:32	announced

Dataset with its publication pending

submitter keyword: TRABID

Ruey-HwaChen
contact affiliation	Institute of Biological Chemistry
contact email	rhchen@gate.sinica.edu.tw
lab head
CHENHAN-HSIUN
contact affiliation	research assistant
contact email	harry850590@yahoo.com.tw
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD035002
     1. Label: PRIDE project
     2. Name: Identification of potential substrates of TRABID in HeLa cells using SILAC