PXD038406

PXD038406 is an original dataset announced via ProteomeXchange.

Title	Atrogin-1 regulates BiP levels - novel therapeutic targets for Duchenne Muscular Dystrophy
Description	Skeletal muscle wasting results from numerous pathological conditions impacting both the musculoskeletal and nervous systems. A unifying feature of these pathologies is the upregulation of members of the E3 ubiquitin ligase family, resulting in increased proteolytic degradation of target proteins. Despite the critical role E3 ubiquitin ligases in regulating muscle mass, the specific proteins they target for degradation and the mechanisms by which they regulate skeletal muscle homeostasis remain ill-defined. Here, using zebrafish loss of function models combined with in vivo cell biology and proteomic approaches, we identified the endoplasmic reticulum chaperone, BiP, as a novel target of the E3 ubiquitin ligase atrogin-1. A loss in atrogin-1 results in an accumulation of BiP, leading to impaired mitochondrial dynamics and a subsequent loss in muscle fibre integrity. We further implicate a disruption in atrogin-1 mediated BiP regulation in the pathogenesis of Duchenne Muscular Dystrophy. We reveal that BiP is not only upregulated in Duchenne Muscular Dystrophy, but its inhibition using pharmacological strategies, or by upregulating atrogin-1, significantly ameliorates pathology in a zebrafish model of Duchenne Muscular Dystrophy. Collectively, our data implicates a novel disease axis in the pathogenesis of Duchenne Muscular Dystrophy, and highlights atrogin-1’s essential role in maintaining muscle homeostasis.
HostingRepository	PRIDE
AnnounceDate	2024-03-07
AnnouncementXML	Submission_2024-03-07_05:02:49.258.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Joel Steele
SpeciesList	scientific name: Danio rerio (Zebrafish) (Brachydanio rerio); NCBI TaxID: 7955;
ModificationList	acetylated residue; monohydroxylated residue; iodoacetamide derivatized residue
Instrument	Q Exactive HF

Revision	Datetime	Status	ChangeLog Entry
0	2022-11-26 04:15:25	ID requested
⏵ 1	2024-03-07 05:02:49	announced

Dataset with its publication pending

submitter keyword: Atrogin-1

BiP

Duchenne Muscular Dystrophy;zebrafish

Avnika A. Ruparelia
contact affiliation	Australian Regenerative Medicine Institute, Monash University, Wellington Road, Clayton, VIC 3800, Australia
contact email	Avnika.ruparelia@monash.edu
lab head
Joel Steele
contact affiliation	Monash
contact email	joel.steele@monash.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/2024/03/PXD038406

PRIDE project URI

• PRIDE
  1. PXD038406
     1. Label: PRIDE project
     2. Name: Atrogin-1 regulates BiP levels - novel therapeutic targets for Duchenne Muscular Dystrophy