PXD021232

PXD021232 is an original dataset announced via ProteomeXchange.

Title	Cancer-cell-secreted miR-122 suppresses O-GlcNAcylation to promote muscle proteolysis
Description	Decline in skeletal muscle mass and lower muscular strength are prognostic factors in advanced human cancers. We found that breast cancer suppressed O-linked N-acetylglucosamine (O-GlcNAc) protein modification in skeletal muscle through extracellular-vesicle-encapsulated miR-122 that targeted O-GlcNAc transferase (OGT). Specifically, O-GlcNAcylation of ryanodine receptor 1 (RYR1) Ca2+ release channel competed with NEK10-mediated phosphorylation and increased K48-linked ubiquitination and proteasomal degradation, whereas O-GlcNAcylation of sarco/endoplasmic reticulum Ca2+-ATPase (SERCA3) increased K63-linked ubiquitination and elevated protein level. Muscular protein O-GlcNAcylation was regulated by hypoxia and lactate through HIF1A-dependent OGT promoter activation, and elevated after exercise. Suppressed O-GlcNAcylation in the setting of cancer, especially through increased RYR1 protein, led to Ca2+ leak and calpain protease activation to trigger myofibrillar protein cleavage. This was associated with reduced skeletal muscle mass and contractility in tumor-bearing mice. Our findings link O-GlcNAcylation to muscular protein homeostasis and contractility, and reveal a mechanism of cancer-associated muscle dysregulation.
HostingRepository	PRIDE
AnnounceDate	2023-11-14
AnnouncementXML	Submission_2023-11-14_08:27:37.922.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Majid Ghassemian
SpeciesList	scientific name: Mus musculus (Mouse); NCBI TaxID: 10090;
ModificationList	carbamoylated residue
Instrument	Orbitrap Fusion Lumos

Revision	Datetime	Status	ChangeLog Entry
0	2020-09-01 00:33:02	ID requested
1	2023-03-10 15:51:06	announced
⏵ 2	2023-11-14 08:27:40	announced	2023-11-14: Updated project metadata.

Yan W, Cao M, Ruan X, Jiang L, Lee S, Lemanek A, Ghassemian M, Pizzo DP, Wan Y, Qiao Y, Chin AR, Duggan E, Wang D, Nolan JP, Esko JD, Schenk S, Wang SE, Cancer-cell-secreted miR-122 suppresses O-GlcNAcylation to promote skeletal muscle proteolysis. Nat Cell Biol, 24(5):793-804(2022) [pubmed]

ProteomeXchange project tag: Biology/Disease-Driven Human Proteome Project (B/D-HPP), Human Proteome Project

submitter keyword: mouse cancer glycosylation

Emily Wang1
contact affiliation	1Department of Pathology; University of California San Diego; La Jolla, CA 92093; USA
contact email	emilywang@ucsd.edu
lab head
Majid Ghassemian
contact affiliation	Scientist
contact email	mghassem@ucsd.edu
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/2023/03/PXD021232

PRIDE project URI

• PRIDE
  1. PXD021232
     1. Label: PRIDE project
     2. Name: Cancer-cell-secreted miR-122 suppresses O-GlcNAcylation to promote muscle proteolysis