A novel DAG-dependent mechanism links PKCa and Cyclin B1 regulating cell cycle progression
Poli, Alessandro; Ramazzotti, Giulia; Matteucci, Alessandro; Manzoli, Lucia; Lonetti, Annalisa; Suh, Pann-Ghill; McCubrey, James A.; Cocco, Lucio
Through the years, different studies showed the involvement of Protein Kinase C (PKC) in cell cycle control, in particular during G1/S transition. Little is known about their role at G2/M checkpoint. In this study, using K562 human erythroleukemia cell line, we found a novel and specific mechanism through which the conventional isoform PKC⍺ positively affects Cyclin B1 modulating G2/M progression of cell cycle. Since the kinase activity of this PKC isoform was not necessary in this process, we demonstrated that PKC⍺, physically interacting with Cyclin B1, avoided its degradation and stimulated its nuclear import at mitosis. Moreover, the process resulted to be strictly connected with the increase in nuclear diacylglycerol levels (DAG) at G2/M checkpoint, due to the activity of nuclear Phospholipase C β1 (PLCβ1), the only PLC isoform mainly localized in the nucleus of K562 cells. Taken together, our findings indicated a novel DAG dependent mechanism able to regulate the G2/M progression of the cell cycle.
Poli, Alessandro, & Ramazzotti, Giulia, & Matteucci, Alessandro, & Manzoli, Lucia, & Lonetti, Annalisa, & Suh, Pann-Ghill, & McCubrey, James A., & Cocco, Lucio. (November 2014). A novel DAG-dependent mechanism links PKCa and Cyclin B1 regulating cell cycle progression. Oncotarget, 5(22), 11526- 11540. Retrieved from http://hdl.handle.net/10342/5667
Poli, Alessandro, and Ramazzotti, Giulia, and Matteucci, Alessandro, and Manzoli, Lucia, and Lonetti, Annalisa, and Suh, Pann-Ghill, and McCubrey, James A., and Cocco, Lucio. "A novel DAG-dependent mechanism links PKCa and Cyclin B1 regulating cell cycle progression". Oncotarget. 5:22. (11526-11540), November 2014. February 22, 2019. http://hdl.handle.net/10342/5667.
Poli, Alessandro and Ramazzotti, Giulia and Matteucci, Alessandro and Manzoli, Lucia and Lonetti, Annalisa and Suh, Pann-Ghill and McCubrey, James A. and Cocco, Lucio, "A novel DAG-dependent mechanism links PKCa and Cyclin B1 regulating cell cycle progression," Oncotarget 5, no. 22 (November 2014), http://hdl.handle.net/10342/5667 (accessed February 22, 2019).
Poli, Alessandro, Ramazzotti, Giulia, Matteucci, Alessandro, Manzoli, Lucia, Lonetti, Annalisa, Suh, Pann-Ghill, McCubrey, James A., Cocco, Lucio. A novel DAG-dependent mechanism links PKCa and Cyclin B1 regulating cell cycle progression. Oncotarget. November 2014; 5(22): 11526-11540. http://hdl.handle.net/10342/5667. Accessed February 22, 2019.