# The Less Known Cyclins--Uncovered
## 2 Cyclin C  
Cyclin C is a protein encoded by the CCNC gene, which is located in position 16.2 on chromosome 6. The cyclin belongs to the subfamily of transcriptional cyclins. It was first isolated as a G1 growth factor along with cyclins D and E [5; 6]. It consists of 283 amino acids, while its molecular weight is 33.2 kDa [5; 6]. Cyclin C contains two 5 \(\alpha\)-helix cyclin boxes. It has no additional carboxyl and amino \(\alpha\)-helical regions on the C-terminal domain. The N-terminal domain is not included in the \(\alpha\)-helix cyclin box and is mobile. Human cyclin C binds to Cdk8 through HC \(\alpha\)-helix and activates it [7]. In normal cells, cyclin C is involved in the regulation of the transcription process mainly in two ways. First, cyclin C together with Cdk8, mediator complex subunit 12 (Med12) and mediator complex subunit 13 (Med13) create the Cdk8-dependent kinase module (CKM). CKM is a part of the mediator complex involved in the regulation of the transcription process by phosphorylation of the C-terminal domain (CTD) of RNA polymerase II (RNAPII) [7]. Second, cyclin C in complex with Cdk8 can regulate the transcription process by targeting cyCH-Cdk7 of the transcription factor II Human (TFIIH). Triggered by cyclin C, Cdk8 phosphorylates cyclin H, which results in the limitation of TFIIH ability to activate transcription and inhibition of CTD [8]. Moreover, after induction of various stress types, i.e., oxidative stress, osmotic stress, heat shock or ethanol treatment, cyC-Cdk8 affects stress response genes, transcription of which is required for cell survival after injury [9]. Another function of cyclin C in normal cells is a transmission of the oxidative stress signal to the mitochondria by inducing extensive mitochondrial fragmentation. The induced fraction of cyclin C is released from the nucleus into the cytosol, where it activates the mitochondrial Dynamain related protein 1 (Drp1) GTPase. The result is a fragmentation of the mitochondria, which regulates further stress reactions, i.e., mitophagy or apoptosis [10]. [PERSON] et al., 2015 [11] used mouse embryonic fibroblasts (MEF), treated with cisplatin and H\({}_{2}\)O\({}_{2}\), which led to the induction of oxidative stress. The result was a translocation of cyclin C from the nucleus to the mitochondria, where it connects to Drp1 and is required to initiate the mitochondrial fission. In the same study, the authors showed that cyclin C is also involved in the regulation of apoptosis. After using cisplatin, the results confirmed that the MEF CCNC \(-/-\) cells were characterized by a significant reduction in the Annexin V signal when compared to the wild-type control cells. This suggests that cyclin C results in a cisplatin resistance phenotype and is required for the programmed death in MEF. Simultaneously, after the use of H\({}_{2}\)O\({}_{2}\), MEF CCNC \(-/-\) cells were more resistant than the control cells [11]. In normal cells, cyclin C in the complex with Cdk3 is also involved in the cell's exit from the G0 phase through phosphorylation of the retinoblastoma protein (Rb), which was proved by [PERSON] and [PERSON] in their studies on human fibroblasts. The results suggest that the regulation of re-entry into the cell cycle from the G0 phase is closely correlated with the transcriptional machinery. The authors confirmed that phosphorylation of pRb by cyC-Cdk3 allows the exit from G0 phase, but also limits suppression of rRNA synthesis [12]. Furthermore, [PERSON] et al., 2010 [13] in their studies showed that cyclin C can regulate the G0/G1 transition in human hematopoietic stem/progenitor cells (HSPC). In turn, the silencing of CCNC expression in HSPC results in enhanced expansion and increases their engrafttability in immunodeficient mice treated with sublethal doses of radiation [13]. In normal cells, it is assumed that cyclin C also participates in the regulation of G1 and G2 phases.