PXD002011

PXD002011 is an original dataset announced via ProteomeXchange.

Title	Mutations to the ALS/FTD gene CCNF reveals elevated Lys48-linked ubiquitination by the SCF(cyclin F) complex
Description	Approximately 10% of Amyotrophic lateral sclerosis (ALS) cases have a positive family history (familial ALS) and appear clinically indistinguishable from sporadic cases. ALS and frontotemporal dementia (FTD) are fatal neurodegenerative disorders that have common molecular and pathogenic characteristics; however, their biological mechanisms remain poorly understood. We have previously identified CCNF missense mutations in cohorts of familial and sporadic ALS and FTD cases [ref]. CCNF encodes cyclin F, a component of an E3 ubiquitin-protein ligase (SCFCyclin F) complex that is responsible for ubiquitinating proteins for degradation by the Ubiquitin-Proteasome System (UPS). The SCFCyclin F complex is essential for maintaining cellular homeostasis in cells; but mutations appear to lead to aberrant motor neuron development and neuron degeneration. We revealed elevated Lys48-specific ubiquitination of proteins in neuronal cells expressing mutant CCNFS621G compared to the CCNFWT control, which is consistent with increased Lys48-specific E3 ligase activity of cyclin FS621G (>1.3-fold). Different subsets of immunoprecipitated Lys48-ubiquitinated proteins were identified between CCNFWT and CCNFS621G cells indicating that transfected cyclin F contribute to the protein ubiquitination profile. These findings provide mechanistic insights into the effects of CCNF gene mutations on the function of the SCFcyclin F complex on neuronal proteostasis.
HostingRepository	PRIDE
AnnounceDate	2017-12-01
AnnouncementXML	Submission_2017-12-01_07:52:41.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Albert Lee
SpeciesList	scientific name: Mus musculus (Mouse); NCBI TaxID: 10090;
ModificationList	ubiquitination signature dipeptidyl lysine; acetylated residue; deamidated residue; iodoacetamide derivatized residue
Instrument	Q Exactive; LTQ Orbitrap Elite

Revision	Datetime	Status	ChangeLog Entry
0	2015-04-02 01:00:15	ID requested
⏵ 1	2017-12-01 07:52:42	announced

Lee A, Rayner SL, Gwee SSL, De Luca A, Shahheydari H, Sundaramoorthy V, Ragagnin A, Morsch M, Radford R, Galper J, Freckleton S, Shi B, Walker AK, Don EK, Cole NJ, Yang S, Williams KL, Yerbury JJ, Blair IP, Atkin JD, Molloy MP, Chung RS, Pathogenic mutation in the ALS/FTD gene, CCNF, causes elevated Lys48-linked ubiquitylation and defective autophagy. Cell Mol Life Sci, 75(2):335-354(2018) [pubmed]

curator keyword: Biomedical

submitter keyword: motor neurone disease, ALS, CCNF, ubiquitin

Albert Lee
contact affiliation	Australian Proteome Analysis Facility, Macquarie University, North Ryde, NSW, 2109, Australia
contact email	albert.lee@mq.edu.au
lab head
Albert Lee
contact affiliation	Macquarie University
contact email	albert.lee@mq.edu.au
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD002011
     1. Label: PRIDE project
     2. Name: Mutations to the ALS/FTD gene CCNF reveals elevated Lys48-linked ubiquitination by the SCF(cyclin F) complex