SCYL1-BP1 Affects Cell Cycle Arrest in Human Hepatocellular Carcinoma Cells via Cyclin F and RRM2

Title:SCYL1-BP1 Affects Cell Cycle Arrest in Human Hepatocellular Carcinoma Cells via Cyclin F and RRM2

Volume: 16 Issue: 4

Author(s): Yang Wang, Qiaoming Zhi, Qin Ye, Chengyuan Zhou, Lei Zhang, Wei Yan, Qun Wu, Di Zhang, Pu Li and Keke Huo

Affiliation:

Keywords: Cell cycle, cyclin F, regulation, RRM2, SCYL1-BP1, ubiquitination.

Abstract: The cell cycle is regulated via important biological mechanisms. Controlled expression of cell cycle regulatory proteins is crucial to maintain cell cycle progression. However, unbalanced protein expression leads to many diseases, such as cancer. Previous research suggests that SCYL1-BP1 function might be related to cell cycle progression and SCYL1-BP1 dysfunction to diseases through undefined mechanisms. In this research, an unbiased yeast two-hybrid screen was used to find protein(s) with potential biological relevance to SCYL1-BP1 function, and a novel interaction was recognized between SCYL1-BP1 and Cyclin F. This interaction was chosen as a paradigm to study SCYL1-BP1 function in cell cycle progression and its possible role in tumorigenesis. We found that SCYL1-BP1 binds to Cyclin F both in vivo and in vitro. SCYL1-BP1 overexpression promoted expression of the CCNF gene and simultaneously delayed Cyclin F protein degradation. SCYL1-BP1 knockdown reduced the expression of endogenous Cyclin F. It was also demonstrated in functional assays that SCYL1-BP1 overexpression induces G2/M arrest in cultured liver cells. Furthermore, SCYL1-BP1 sustained RRM2 protein expression by reducing its ubiquitination. Thus, we propose that SCYL1- BP1 affects the cell cycle through increasing steady state levels of Cyclin F and RRM2 proteins, thus constituting a dual regulatory circuit. This study provides a possible mechanism for SCYL1-BP1-mediated cell cycle regulation and related diseases.

Cite this article as:

Wang Yang, Zhi Qiaoming, Ye Qin, Zhou Chengyuan, Zhang Lei, Yan Wei, Wu Qun, Zhang Di, Li Pu and Huo Keke, SCYL1-BP1 Affects Cell Cycle Arrest in Human Hepatocellular Carcinoma Cells via Cyclin F and RRM2, Anti-Cancer Agents in Medicinal Chemistry 2016; 16 (4) . https://dx.doi.org/10.2174/1871520615666150518093814