PXD058272

PXD058272 is an original dataset announced via ProteomeXchange.

Title	An endophyte-derived small molecule targets LIC1 to suppress lung tumor growth by inducing autophagy
Description	Small molecules that induce autophagy in specific biological contexts will provide invaluable chemical probes and potential anti-cancer therapeutics. Herein, we identified a potent autophagy inducer 18e through screening of an endophyte-derived small molecule library. 18e demonstrates significant anti-tumor efficacy in non-small-cell lung cancer (NSCLC) tumors and sensitizes tumor to anti-PD1 immunotherapy. Utilizing a photoaffinity labeling approach, we identified dynein Light Intermediate Chain-1 (LIC1), a subunit of dynein, as the direct target of 18e. Mechanistically, the targeting of LIC1 by 18e markedly disrupts the interactions between LIC1 and stress-sensing effector RUVBL1. This disruption leads to ribosome collision, subsequently activating the downstream GCN2-eIF2α-ATF4 axis-mediated integrated stress response (ISR), which ultimately facilitates autophagic cell death. Our findings not only define LIC1 as a novel therapeutic target for NSCLC, but also underscore the potential of 18e as a promising autophagy inducer for treatment of this disease.
HostingRepository	PRIDE
AnnounceDate	2025-10-20
AnnouncementXML	Submission_2025-10-19_18:45:55.761.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	雷名 吴
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: NEWT:9606;
ModificationList	No PTMs are included in the dataset
Instrument	LCQ Classic

Revision	Datetime	Status	ChangeLog Entry
0	2024-11-26 01:21:14	ID requested
⏵ 1	2025-10-19 18:45:56	announced

10.1038/S41589-025-02040-W;

submitter keyword: Non-small-cell lung cancer，autophagy

Leiming Wu
contact affiliation	School of Pharmaceutical Science, Sun Yat-sen University, China
contact email	wulm27@mail2.sysu.edu.cn
lab head
雷名 吴
contact affiliation	School of Pharmaceutical Science.Sun Yat-sen University
contact email	wulm27@mail2.sysu.edu.cn
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/2025/10/PXD058272

PRIDE project URI

• PRIDE
  1. PXD058272
     1. Label: PRIDE project
     2. Name: An endophyte-derived small molecule targets LIC1 to suppress lung tumor growth by inducing autophagy