@article{mills_wang_bhatt_grimsrud_matson_lahiri_burke_cook_hirschey_emanuele_2021, title={Sirtuin 5 Is Regulated by the SCFCyclin (F) Ubiquitin Ligase and Is Involved in Cell Cycle Control}, volume={41}, ISSN={["1098-5549"]}, DOI={10.1128/MCB.00269-20}, abstractNote={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. ABSTRACT 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.}, number={2}, journal={MOLECULAR AND CELLULAR BIOLOGY}, author={Mills, Christine A. and Wang, Xianxi and Bhatt, Dhaval P. and Grimsrud, Paul A. and Matson, Jacob Peter and Lahiri, Debojyoti and Burke, Daniel J. and Cook, Jeanette Gowen and Hirschey, Matthew D. and Emanuele, Michael J.}, year={2021}, month={Feb} }
 @article{choudhury_bonacci_arceci_lahiri_mills_kernan_branigan_decaprio_burke_emanuele_2016, title={APC/C and SCFcyclin F Constitute a Reciprocal Feedback Circuit Controlling S-Phase Entry}, volume={16}, ISSN={["2211-1247"]}, DOI={10.1016/j.celrep.2016.08.058}, abstractNote={The anaphase promoting complex/cyclosome (APC/C) is an ubiquitin ligase and core component of the cell-cycle oscillator. During G1 phase, APC/C binds to its substrate receptor Cdh1 and APC/C(Cdh1) plays an important role in restricting S-phase entry and maintaining genome integrity. We describe a reciprocal feedback circuit between APC/C and a second ubiquitin ligase, the SCF (Skp1-Cul1-F box). We show that cyclin F, a cell-cycle-regulated substrate receptor (F-box protein) for the SCF, is targeted for degradation by APC/C. Furthermore, we establish that Cdh1 is itself a substrate of SCF(cyclin F). Cyclin F loss impairs Cdh1 degradation and delays S-phase entry, and this delay is reversed by simultaneous removal of Cdh1. These data indicate that the coordinated, temporal ordering of cyclin F and Cdh1 degradation, organized in a double-negative feedback loop, represents a fundamental aspect of cell-cycle control. This mutual antagonism could be a feature of other oscillating systems.}, number={12}, journal={CELL REPORTS}, author={Choudhury, Rajarshi and Bonacci, Thomas and Arceci, Anthony and Lahiri, Debojyoti and Mills, Christine A. and Kernan, Jennifer L. and Branigan, Timothy B. and DeCaprio, James A. and Burke, Daniel J. and Emanuele, Michael J.}, year={2016}, month={Sep}, pages={3359–3372} }