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

Publication ,  Journal Article
Mills, CA; Wang, X; Bhatt, DP; Grimsrud, PA; Matson, JP; Lahiri, D; Burke, DJ; Cook, JG; Hirschey, MD; Emanuele, MJ
Published in: Mol Cell Biol
January 25, 2021

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.

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Published In

Mol Cell Biol

DOI

EISSN

1098-5549

Publication Date

January 25, 2021

Volume

41

Issue

2

Location

United States

Related Subject Headings

  • Ubiquitination
  • Ubiquitin-Protein Ligases
  • Sirtuins
  • Signal Transduction
  • Saccharomyces cerevisiae Proteins
  • Saccharomyces cerevisiae
  • SKP Cullin F-Box Protein Ligases
  • Protein Processing, Post-Translational
  • Mutation
  • Humans
 

Citation

APA
Chicago
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Mills, C. A., Wang, X., Bhatt, D. P., Grimsrud, P. A., Matson, J. P., Lahiri, D., … Emanuele, M. J. (2021). Sirtuin 5 Is Regulated by the SCFCyclin F Ubiquitin Ligase and Is Involved in Cell Cycle Control. Mol Cell Biol, 41(2). https://doi.org/10.1128/MCB.00269-20
Mills, Christine A., Xianxi Wang, Dhaval P. Bhatt, Paul A. Grimsrud, Jacob Peter Matson, Debojyoti Lahiri, Daniel J. Burke, Jeanette Gowen Cook, Matthew D. Hirschey, and Michael J. Emanuele. “Sirtuin 5 Is Regulated by the SCFCyclin F Ubiquitin Ligase and Is Involved in Cell Cycle Control.Mol Cell Biol 41, no. 2 (January 25, 2021). https://doi.org/10.1128/MCB.00269-20.
Mills CA, Wang X, Bhatt DP, Grimsrud PA, Matson JP, Lahiri D, et al. Sirtuin 5 Is Regulated by the SCFCyclin F Ubiquitin Ligase and Is Involved in Cell Cycle Control. Mol Cell Biol. 2021 Jan 25;41(2).
Mills, Christine A., et al. “Sirtuin 5 Is Regulated by the SCFCyclin F Ubiquitin Ligase and Is Involved in Cell Cycle Control.Mol Cell Biol, vol. 41, no. 2, Jan. 2021. Pubmed, doi:10.1128/MCB.00269-20.
Mills CA, Wang X, Bhatt DP, Grimsrud PA, Matson JP, Lahiri D, Burke DJ, Cook JG, Hirschey MD, Emanuele MJ. Sirtuin 5 Is Regulated by the SCFCyclin F Ubiquitin Ligase and Is Involved in Cell Cycle Control. Mol Cell Biol. 2021 Jan 25;41(2).

Published In

Mol Cell Biol

DOI

EISSN

1098-5549

Publication Date

January 25, 2021

Volume

41

Issue

2

Location

United States

Related Subject Headings

  • Ubiquitination
  • Ubiquitin-Protein Ligases
  • Sirtuins
  • Signal Transduction
  • Saccharomyces cerevisiae Proteins
  • Saccharomyces cerevisiae
  • SKP Cullin F-Box Protein Ligases
  • Protein Processing, Post-Translational
  • Mutation
  • Humans