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PXD014163

PXD014163 is an original dataset announced via ProteomeXchange.

Dataset Summary
TitleALS/FTD-causing mutation in cyclin F causes the dysregulation of SFPQ
DescriptionRecently, we identified missense mutations in CCNF that are causative of familial and sporadic amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD). CCNF encodes for cyclin F, a substrate recognition component of an E3-ubiquitin ligase. Mutations in CCNF directly implicates disruption in the ubiquitin-proteasome system in the pathogenesis of ALS/FTD. In this study we used an unbiased proteomic screening workflow using the proximity-based ligation method, BioID, to identify putative interaction partners of cyclin F. In doing so, we found over 100 putative interaction partners of cyclin F. Notably, we demonstrated that cyclin F closely associates with a number of essential paraspeckle proteins, which are stress-responsive proteins that have recently been implicated in ALS pathogenesis. We further demonstrate that SCFcyclin F mediates the direct ubiquitylation and subsequent proteasomal degradation of RBM14, a core component of the paraspeckle complex. This degradation is defective when cyclin F carries an ALS/FTD-causing mutation, leading to RBM14 accumulation in primary neurons upon proteasome inhibition. Additionally, analysis of ALS patient post-mortem tissue revealed that RBM14 levels were significantly reduced in post-mortem ALS patient motor cortex and significantly reduced in the neurons of spinal cord tissue. Together, our data indicate that defects in RBM14 homeostasis, which can be due to defects in cyclin F-mediated degradation, may be a common factor underlying ALS/FTD disease pathogenesis.
HostingRepositoryPRIDE
AnnounceDate2021-03-18
AnnouncementXMLSubmission_2021-03-18_01:19:43.277.xml
DigitalObjectIdentifierhttps://dx.doi.org/10.6019/PXD014163
ReviewLevelPeer-reviewed dataset
DatasetOriginOriginal dataset
RepositorySupportSupported dataset by repository
PrimarySubmitterAlbert Lee
SpeciesList scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationListOxidation; Acetyl; Carbamidomethyl
InstrumentQ Exactive
Dataset History
RevisionDatetimeStatusChangeLog Entry
02019-06-06 08:59:33ID requested
12021-03-18 00:21:58announced
22021-03-18 01:19:44announced2021-03-18: Updated project metadata.
Publication List
Rayner SL, Cheng F, Hogan AL, Grima N, Yang S, Ke YD, Au CG, Morsch M, De Luca A, Davidson JM, Molloy MP, Shi B, Ittner LM, Blair I, Chung RS, Lee A, ALS/FTD-causing mutation in cyclin F causes the dysregulation of SFPQ. Hum Mol Genet, 30(11):971-984(2021) [pubmed]
Keyword List
submitter keyword: BioID, ubiquitylation, proteomics, amyotrophic lateral sclerosis, frontotemporal dementia, paraspeckles, cyclin F, RBM14, homeostasis
Contact List
Albert Lee
contact affiliationDepartment of Biomedical Sciences, Faculty of Medicine and Health Sciences, Macquarie University, North Ryde, NSW 2109
contact emailalbert.lee@mq.edu.au
lab head
Albert Lee
contact affiliationMacquarie University
contact emailalbert.lee@mq.edu.au
dataset submitter
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Dataset FTP location
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