PXD074890

PXD074890 is an original dataset announced via ProteomeXchange.

Title	UFMylation-Dependent Inhibition of AKT Signaling by PHLDA3 in Lung Adenocarcinoma
Description	UFMylation, a recently identified ubiquitin-like modification mediated by the E3 ligase UFL1, plays context-specific roles in cancers, but its substrates and functions in lung adenocarcinoma (LUAD) remain poorly defined. Here, we identify the AKT signaling repressor PHLDA3 as a substrate of UFL1 in LUAD. UFMylation of PHLDA3 at Lys51 and Lys106 promotes its membrane localization, thereby blocking AKT membrane recruitment and suppressing downstream signaling. Tumor-associated PHLDA3 mutations F41L, E82G and K106N impair its UFMylation and membrane translocation, resulting in AKT hyperactivation and enhanced tumor growth. In samples from patients with LUAD, UFL1 expression inversely correlates with phosphor-AKT levels. Functionally, the UFL1-PHLDA3 axis inhibits LUAD progression in both cell line-based and patient-derived xenograft models. These findings define a tumor-suppressive UFMylation pathway that modulates AKT activity and provides a mechanistic rationale for targeting UFL1-PHLDA3 signaling in LUAD.
HostingRepository	PRIDE
AnnounceDate	2026-04-08
AnnouncementXML	Submission_2026-04-08_04:25:30.279.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Xiuqing Ma
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: NEWT:9606;
ModificationList	No PTMs are included in the dataset
Instrument	Q Exactive HF

Revision	Datetime	Status	ChangeLog Entry
0	2026-02-25 03:21:35	ID requested
⏵ 1	2026-04-08 04:25:30	announced

10.1016/J.CELREP.2026.117154;

submitter keyword: None

Tongzheng Liu
contact affiliation	State Key Laboratory of Bioactive Molecules and Druggability Assessment/International Cooperative Laboratory of Traditional Chinese Medicine Modernization and Innovative Drug Development of Ministry of Education (MOE) of China/College of Pharmacy, Jinan University, Guangzhou, 510632, China
contact email	liutongzheng@jnu.edu.cn
lab head
Xiuqing Ma
contact affiliation	Jinan University
contact email	maxiuqing@stu2024.jnu.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/2026/04/PXD074890

PRIDE project URI

• PRIDE
  1. PXD074890
     1. Label: PRIDE project
     2. Name: UFMylation-Dependent Inhibition of AKT Signaling by PHLDA3 in Lung Adenocarcinoma