Cyclins control cell cycle progression by regulating the activity of cyclin-dependent kinases (Cdks). Cyclin I is a member of the cyclin family because of the presence of a cyclin box motif. It has been suggested that Cyclin I is involved in various biological processes, such as cell survival, angiogenesis, and cell differentiation. However, whether or not Cyclin I has a role in regulating the cell cycle similarly to other cyclins has yet to be clarified. Therefore, we investigated the role for Cyclin I in cell cycle progression. We showed that the protein level of Cyclin I oscillated during the cell cycle, and that Cyclin I was subjected to ubiquitination and degradation in cells. The interaction between Cyclin I and Cdk5 was detected in cells overexpressed with both proteins. Furthermore, depletion of Cyclin I by siRNAs prevented cell proliferation, suggesting the positive role of Cyclin I for the cell cycle progression. In addition, flow cytometric analysis revealed that cells depleted of Cyclin I were accumulated at G₂/M phases. By using HeLa.S-Fucci (fluorescent ubiquitination-based cell cycle indicator) cells, we further confirmed that knockdown of Cyclin I induced cell cycle arrest at S/G₂/M phases. These results strongly suggest that Cyclin I has the role in the regulation of cell cycle progression.
Keywords: Cdk5; Fucci; cell proliferation; cyclin I; ubiquitination.