Sirtuin 5 Is Regulated by the SCFCyclin F Ubiquitin Ligase and Is Involved in Cell Cycle Control.

Journal Article (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, and F-box protein (SCF) family of E3 ubiquitin ligases. Despite its importance in cell cycle progression, identifying cyclin F-bound SCF complex (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 a subsequent increase in both S and G2/M. Global proteomic analyses reveal cyclin-dependent kinase (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

  • January 25, 2021

Published In

Volume / Issue

  • 41 / 2

PubMed ID

  • 33168699

Pubmed Central ID

  • PMC8093487

Electronic International Standard Serial Number (EISSN)

  • 1098-5549

Digital Object Identifier (DOI)

  • 10.1128/MCB.00269-20


  • eng

Conference Location

  • United States