title: A novel DAG-dependent mechanism links PKCɑ and Cyclin B1 regulating cell cycle progression.
abstract: 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 PKCα 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 PKCα, 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.
authors.affiliation: Cell Signaling Laboratory, Department of Biomedical Sciences, University of Bologna, Bologna, Italy.
authors.forename: Alessandro
authors.initials: A
authors.lastname: Poli
authors.affiliation: Cell Signaling Laboratory, Department of Biomedical Sciences, University of Bologna, Bologna, Italy.
authors.forename: Giulia
authors.initials: G
authors.lastname: Ramazzotti
authors.affiliation: CNR-National Research Council of Italy, Institute of Molecular Genetics, Bologna, Italy.
authors.forename: Alessandro
authors.initials: A
authors.lastname: Matteucci
authors.affiliation: Cell Signaling Laboratory, Department of Biomedical Sciences, University of Bologna, Bologna, Italy.
authors.forename: Lucia
authors.initials: L
authors.lastname: Manzoli
authors.affiliation: Cell Signaling Laboratory, Department of Biomedical Sciences, University of Bologna, Bologna, Italy.
authors.forename: Annalisa
authors.initials: A
authors.lastname: Lonetti
authors.affiliation: School of Nano-Biotechnology and Chemical Engineering, Ulsan National Institute of Science and Technology, Ulsan, Republic of Korea.
authors.forename: Pann-Ghill
authors.initials: PG
authors.lastname: Suh
authors.affiliation: Department of Microbiology and Immunology, Brody School of Medicine, East Carolina University, Greenville, NC, USA.
authors.forename: James A
authors.initials: JA
authors.lastname: McCubrey
authors.affiliation: Cell Signaling Laboratory, Department of Biomedical Sciences, University of Bologna, Bologna, Italy.
authors.forename: Lucio
authors.initials: L
authors.lastname: Cocco
mesh_terms: D021581:Active Transport, Cell Nucleus; D002453:Cell Cycle; D045744:Cell Line, Tumor; D002467:Cell Nucleus / Q000378:metabolism; D002469:Cell Separation; D056744:Cyclin B1 / Q000378:metabolism*; D004075:Diglycerides / Q000737:chemistry*; D005434:Flow Cytometry; D006801:Humans; D007527:Isoenzymes / Q000378:metabolism; D020014:K562 Cells; D008856:Microscopy, Fluorescence; D008938:Mitosis; D054799:Phospholipase C beta / Q000378:metabolism; D051571:Protein Kinase C-alpha / Q000378:metabolism*
chemical_list: C534699:CCNB1 protein, human; D056744:Cyclin B1; D004075:Diglycerides; D007527:Isoenzymes; C496628:PRKCA protein, human; D051571:Protein Kinase C-alpha; C518033:PLCB1 protein, human; D054799:Phospholipase C beta