PXD030729

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

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PRIDE project URI

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