# The Less Known Cyclins--Uncovered
## 6 Cyclin I  
Cyclin I is encoded by the CCNI gene localized in position 21.1 on the human chromosome 4. The protein consists of 377 amino acids with a total molecular weight of 42.6 kDa. Cyclin I was first isolated from the human forebrain cortex obtained from an equalized cDNA library. The protein is characterized by the classic cyclin construction, where the N-terminal domain contains a \"cyclin box\", while the PEST sequence is on the C-terminal domain. The protein has significant structural similarity in the N-terminal domain with cyclins G and E, while in C-terminal only with cyclin G. High expression of cyclin I was demonstrated in postmitotic tissues, for example, heart, brain and skeletal muscle. Furthermore, cyclin I binds to the Cdk5 and activates it. In turn, activated Cdk5 plays a key role in postmitotic neurons, through participation in synaptic signaling, neuron development and migration. Moreover, the protein is a pivotal factor in the process of angiogenesis, cell differentiation and survival [53; 54]. Initial research conducted by [PERSON] et al., 1995 [53] indicated that there is no relationship between the expression of cyclin I and the regulation of cell cycle as its mRNA level does not fluctuate during the cell cycle [53]. However, the results of [PERSON] et al., 2013 [54] suggest that cyclin I is involved in the progression of the cell cycle. The authors showed that along with the decrease in the expression of cyclin I, cell proliferation stopped, which was a result of the inhibition of the cell cycle in S and G2/M phases. These results may also suggest that cyclin I participates in control of the DNA replication process [54]. Another function of cyclin I in normal cells is the protection of podocytes from apoptosis after mitosis. As proven by [PERSON] et al., 2006 [55] maintaining the correct expression of cyclin I is extremely important for the proper functioning of podocytar cells and thus preventing the progression of kidney diseases and glomerulosclerosis. However, other studies showed that cyclin I \(-/-\) cells are more susceptible to apoptosis in vitro and in vivo. This is related to the p21 Cip1/Waf1 inhibitor, which action is regulated by cyclin I; p21 Cip1/Waf1 interacts with proaspase-3 preventing its activation, which precludes the initiation of the apoptosis execution-phase [55]. In turn, elevated levels of cyclin I are associated with the final arrest of the growth of cardiomyocytes. [PERSON] et al., 2007 [56] used 2-day-old cardiomyocytes and cardiomyocytes isolated from 13-day-old postnatal hearts of mice to assess the changes in cyclin I expression profile along with aging. It demonstrated that the expression level of cyclin I was significantly higher in 13-day-old cardiomyocytes. After studying the expression pattern of cyclin I in the H9c2 cell line (rat myoblasts), it was found that the expression of cyclin was relatively low during the growth phase and increased in the growth arrest/differentiation stop phase, which confirms the results of the previous studies [56]. In addition, in the case of cancer cells, expression of cyclin I is correlated with proliferative activity and angiogenesis. As indicated by research carried out by [PERSON] et al., 2015 [57] increased cyclin I expression may promote the development of cisplatin resistance in cervical cancer (CC). The authors showed that cyclin I is overexpressed in CC cells resistant to cisplatin chemotherapy. They also confirmed that the increased level of cyclin I expression stimulates the growth of tumor cells in vitro and enhances the resistance of the tumor cells to cisplatin in vivo. This is probably due to the antiapoptotic action of cycl-Cdk5 [57]. However, overexpression of cyclin I may also promote tumor development by its participation in the angiogenesis process. [PERSON] et al., 2012 [58] confirmed the association of cyclin I with vascular endothelial growth factor (VEGF) and 2 VEGF receptor (VEGF-2), which in turn leads to angiogenesis, providing epithelial ovarian cancer cells a proliferative advantage.