PXD019396

PXD019396 is an original dataset announced via ProteomeXchange.

Title	SCFCyclin F targets the metabolic protein Sirtuin 5 for ubiquitination
Description	Cell cycle transitions are regulated by a number of coordinating signaling events. The ubiquitin-proteasome system is an important part of this cell cycle signaling. Cyclin F, a substrate adapter for the SCF (SKP1/CUL1/F-box) E3 ubiquitin ligase, is an important regulator of cell cycle progression. However, identifying SCFCyclin F substrates important for the G1-S transition and other cell cycle events has remained technically challenging. Since Cyclin F overexpression rescues a yeast mutant in the cdc4 gene, we considered the possibility that other genes that genetically modify cdc4 mutant lethality could also encode Cyclin F substrates. We identified the mitochondrial and cytosolic deacylating enzyme Sirtuin 5 (SIRT5) as a novel Cyclin F substrate. SIRT5 has been implicated in a number of metabolic processes, but its connection to the cell cycle is not known. Here, we demonstrate the ability of Cyclin F to interact with, ubiquitinate and control the abundance and stability of SIRT5. Since previously identified Cyclin F targets are important for cell cycle progression, we hypothesized that SIRT5 would influence cell cycle progression. We show SIRT5 CRISPR knockout results in a diminished G1 population, and subsequent increase in both S and G2/M. Proteomic analyses reveal CDK signaling changes congruent with the cell cycle changes in SIRT5 knockout cells. Together these data demonstrate SIRT5 is regulated by Cyclin F and suggest a connection between SIRT5, cell cycle regulation, and metabolism.
HostingRepository	jPOST
AnnounceDate	2020-11-17
AnnouncementXML	Submission_2022-09-18_03:51:34.160.xml
DigitalObjectIdentifier
ReviewLevel	Non peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Paul Grimsrud
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	S-carboxamidomethyl-L-cysteine; O-phospho-L-serine; O-phospho-L-threonine; O4'-phospho-L-tyrosine; L-methionine sulfoxide; TMT6plex reporter+balance reagent N-acylated residue; TMT6plex reporter+balance reagent acylated N-terminal
Instrument	Q Exactive

Revision	Datetime	Status	ChangeLog Entry
0	2020-05-26 13:06:26	ID requested
1	2020-11-17 06:18:42	announced
2	2021-02-04 16:56:41	announced	2021-02-04: Updated FTP location.
⏵ 3	2022-09-18 03:51:34	announced	2022-09-18: Updated FTP location.

Dataset with its publication pending

submitter keyword: Cyclin F (CCNF), Sirtuin 5 (SIRT5), cell cycle, ubiquitin, metabolism

Matthew D. Hirschey
lab head
Paul Grimsrud
contact affiliation	Duke University
dataset submitter

jPOST dataset URI

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