Sirtuin 5 is Regulated by the SCF-Cyclin F Ubiquitin Ligase and is Involved in Cell Cycle Control.

Published online

Journal Article

The ubiquitin-proteasome system is essential for cell cycle progression. Cyclin F is a cell cycle regulated substrate adapter F-box protein for the SKP1/CUL1/F-box (SCF) family of E3 ubiquitin ligases. Despite its importance in cell cycle progression, identifying SCFCyclin F substrates has remained 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 metabolic processes, but its connection to the cell cycle is not known. We show that Cyclin F interacts with, and controls the ubiquitination, abundance, and stability of SIRT5. We show SIRT5 knockout results in a diminished G1 population, and subsequent increase in both S and G2/M. Global proteomic analyses reveal CDK signaling changes congruent with the cell cycle changes in SIRT5 knockout cells. Together these data demonstrate that SIRT5 is regulated by Cyclin F and suggest a connection between SIRT5, cell cycle regulation, and metabolism.

Full Text

Duke Authors

Cited Authors

  • Mills, CA; Wang, X; Bhatt, DP; Grimsrud, PA; Matson, JP; Lahiri, D; Burke, DJ; Cook, JG; Hirschey, MD; Emanuele, MJ

Published Date

  • November 9, 2020

Published In

PubMed ID

  • 33168699

Pubmed Central ID

  • 33168699

Electronic International Standard Serial Number (EISSN)

  • 1098-5549

Digital Object Identifier (DOI)

  • 10.1128/MCB.00269-20

Language

  • eng

Conference Location

  • United States