Cyclin-F

Definition:

Substrate recognition component of a SCF (SKP1-CUL1-F-box protein) E3 ubiquitin-protein ligase complex which mediates the ubiquitination and subsequent proteasomal degradation of target proteins. The SCF(CCNF) E3 ubiquitin-protein ligase complex is an integral component of the ubiquitin proteasome system (UPS) and links proteasome degradation to the cell cycle. Mediates the substrate recognition and the proteasomal degradation of various target proteins involved in the regulation of cell cycle progression and in the maintenance of genome stability. Mediates the ubiquitination and proteasomal degradation of CP110 during G2 phase, thereby acting as an inhibitor of centrosome reduplication. In G2, mediates the ubiquitination and subsequent degradation of ribonucleotide reductase RRM2, thereby maintaining a balanced pool of dNTPs and genome integrity. In G2, mediates the ubiquitination and proteasomal degradation of CDC6, thereby suppressing DNA re-replication and preventing genome instability. Involved in the ubiquitination and degradation of the substrate adapter CDH1 of the anaphase-promoting complex (APC/C), thereby acting as an antagonist of APC/C in regulating G1 progression and S phase entry. May play a role in the G2 cell cycle checkpoint control after DNA damage, possibly by promoting the ubiquitination of MYBL2/BMYB.

References:

[1]. David Walter, et al. SCF(Cyclin F)-dependent degradation of CDC6 suppresses DNA re-replication. Nat Commun. 2016 Jan 28;7:10530. [Content Brief]

[2]. Kelly L Williams, et al. CCNF mutations in amyotrophic lateral sclerosis and frontotemporal dementia. Nat Commun. 2016 Apr 15;7:11253. [Content Brief]

[3]. Ditte Kjærsgaard Klein, et al. Cyclin F suppresses B-Myb activity to promote cell cycle checkpoint control. Nat Commun. 2015 Jan 5;6:5800. [Content Brief]

[4]. C Bai, et al. SKP1 connects cell cycle regulators to the ubiquitin proteolysis machinery through a novel motif, the F-box. Cell. 1996 Jul 26;86(2):263-74. [Content Brief]

[5]. Rajarshi Choudhury, et al. APC/C and SCF(cyclin F) Constitute a Reciprocal Feedback Circuit Controlling S-Phase Entry. Cell Rep. 2016 Sep 20;16(12):3359-3372. [Content Brief]

[6]. Vincenzo D'Angiolella, et al. SCF(Cyclin F) controls centrosome homeostasis and mitotic fidelity through CP110 degradation. Nature. 2010 Jul 1;466(7302):138-42. [Content Brief]

[7]. Vincenzo D'Angiolella, et al. Cyclin F-mediated degradation of ribonucleotide reductase M2 controls genome integrity and DNA repair. Cell. 2012 May 25;149(5):1023-34. [Content Brief]

[8]. Albert Lee, et al. Pathogenic mutation in the ALS/FTD gene, CCNF, causes elevated Lys48-linked ubiquitylation and defective autophagy. Cell Mol Life Sci. 2018 Jan;75(2):335-354. [Content Brief]

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