PXD030729-1

PXD030729 is an original dataset announced via ProteomeXchange.

Title	Identification of CCNF/Cyclin F targets
Description	The founding member of the F-box protein family, Cyclin F, serves as substrate adaptor for the Ubiquitin E3 ligase Skp1-Cul1-F-box (SCF)Cyclin F which is responsible for ubiquitination of proteins involved in cell cycle progression, DNA damage and mitotic fidelity. Missense mutations in CCNF encoding for Cyclin F are associated with amyotrophic lateral sclerosis (ALS). However, it remains elusive whether CCNF mutations affect the substrate adaptor function of Cyclin F and whether altered SCFCyclin F mediated ubiquitination contributes to ALS pathogenesis in CCNF mutation carrier. To start addressing these questions, we set out to identify new SCFCyclin F targets in neuronal and patient-derived cells. Mass spectrometry-based ubiquitinome profiling of CCNF knockout and mutant cell lines as well as Cyclin F proximity and interaction proteomics converged on the HSP90 chaperone machinery as new substrate candidate. Biochemical analyses confirmed the Cyclin F dependent binding and ubiquitination of HSP90AB1 and unveiled a regulatory role of this ubiquitination in controlling the binding of a number of HSP90 clients and co-factors, thereby implying chaperone dysregulation and CCNF loss-of-function mechanism in ALS.
HostingRepository	PRIDE
AnnounceDate	2022-09-14
AnnouncementXML	Submission_2022-09-13_16:16:18.242.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Christian Behrends
SpeciesList	scientific name: Mus musculus (Mouse); NCBI TaxID: 10090; scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	carbamoylated residue; ubiquitinylated lysine; acetylated residue
Instrument	Q Exactive HF

Revision	Datetime	Status	ChangeLog Entry
0	2022-01-05 01:38:02	ID requested
⏵ 1	2022-09-13 16:16:18	announced

Dataset with its publication pending

submitter keyword: LC-MS, Human, Mouse, ALS, CCNF, Cyclin F

Christian Behrends
contact affiliation	Munich Cluster for Systems Neurology (SyNergy) Ludwig-Maximilians-University Munich, Germany
contact email	christian.behrends@mail03.med.uni-muenchen.de
lab head
Christian Behrends
contact affiliation	SyNergy, LMU München
contact email	christian.behrends@mail03.med.uni-muenchen.de
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/2022/09/PXD030729

PRIDE project URI

• PRIDE
  1. PXD030729
     1. Label: PRIDE project
     2. Name: Identification of CCNF/Cyclin F targets