PXD055376

PXD055376 is an original dataset announced via ProteomeXchange.

Title	Nucleus-Translocated GCLM Promotes Chemoresistance in Colorectal Cancer through a Moonlighting Function
Description	Emerging evidence indicates that metabolic enzymes perform moonlighting functions during tumor progression, including the modulation of chemoresistance. However, the underlying mechanisms of these functions remain elusive. In this study, utilizing a metabolic CRISPR-Cas9 knockout library screen, we observed that loss of Glutamate-cysteine ligase modifier subunit (GCLM), a rate-limiting enzyme in glutathione biosynthesis, noticeably heightens the sensitivity of colorectal cancer (CRC) cells to platinum-based chemotherapy. Mechanistically, we unveil a noncanonical mechanism through which nuclear GCLM competitively interacts with NF-kappa-B-repressing factor (NKRF), a known inhibitor of NF-κB signaling, to promote NF-κB activity and subsequently facilitate chemoresistance. In response to platinum drug treatment, P38 MAPK phosphorylates GCLM at T17, resulting in its recognition by importin a5 and subsequent nuclear translocation. Furthermore, elevated expression of nuclear GCLM correlates with unfavorable prognosis and poor benefit from standard chemotherapy. Overall, our work shed light on the essential nonmetabolic role and posttranslational regulatory mechanism of GCLM in enhancing NF-κB activity and subsequent chemoresistance.
HostingRepository	PRIDE
AnnounceDate	2024-11-15
AnnouncementXML	Submission_2024-11-14_21:55:18.456.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Jinfei Lin
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	No PTMs are included in the dataset
Instrument	Q Exactive

Revision	Datetime	Status	ChangeLog Entry
0	2024-08-30 00:43:19	ID requested
⏵ 1	2024-11-14 21:55:18	announced

Dataset with its publication pending

submitter keyword: Nuclear GCLM

Moonlighting function

NKRF

Phosphorylation

Chemoresistance;LC-MS/MS

Jin-fei Lin
contact affiliation	Department of Clinical Laboratory, Sun Yat-Sen University Cancer Center, Guangzhou 510060, P. R. China.
contact email	linjf@sysucc.org.cn
lab head
Jinfei Lin
contact affiliation	Sun Yat-sen University Cancer Center
contact email	linjf@sysucc.org.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/2024/11/PXD055376

PRIDE project URI

• PRIDE
  1. PXD055376
     1. Label: PRIDE project
     2. Name: Nucleus-Translocated GCLM Promotes Chemoresistance in Colorectal Cancer through a Moonlighting Function