title: Cyclin D1 inhibits mitochondrial activity in B cells.
abstract: Cyclin D1 is a cell cycle regulatory protein that acts at the G1-S transition, following its binding to and activation by the cyclin-dependent kinases 4 or 6. Cyclin D1 is absent from the entire B-cell lineage but is present in a large percentage of 2 types of malignant B-cell hemopathy--mantle cell lymphoma and multiple myeloma--suggesting a major role of this protein in the malignancy process. We show here, in an experimental model of cyclin D1 fusion protein transduction in mature B cells, that, cyclin D1 inhibits total mitochondrial activity. Cyclin D1 is localized at the outer mitochondrial membrane, bound to a voltage-dependent anion channel through its central domain, and it competes with hexokinase 2 for binding to this channel. The bound cyclin D1 decreases the supply of ADP, ATP, and metabolites, thereby reducing energy production. This function of cyclin D1 was also reported by others in normal and transformed mammary epithelial cells, suggesting that it may be ubiquitous.
authors.affiliation: Biologie Moléculaire et Cellulaire de la Signalisation, EA 3919, UFR de médecine, IFR 146, Université de Caen, Caen, France.
authors.forename: Guergana
authors.initials: G
authors.lastname: Tchakarska
authors.forename: Mikel
authors.initials: M
authors.lastname: Roussel
authors.forename: Xavier
authors.initials: X
authors.lastname: Troussard
authors.forename: Brigitte
authors.initials: B
authors.lastname: Sola
mesh_terms: D001402:B-Lymphocytes / Q000378:metabolism*; D015153:Blotting, Western; D002460:Cell Line; D049109:Cell Proliferation; D002469:Cell Separation; D019938:Cyclin D1 / Q000378:metabolism*; D005434:Flow Cytometry; D005455:Fluorescent Antibody Technique; D006801:Humans; D047468:Immunoprecipitation; D053078:Membrane Potential, Mitochondrial / Q000502:physiology; D018613:Microscopy, Confocal; D008928:Mitochondria / Q000378:metabolism*; D011993:Recombinant Fusion Proteins / Q000378:metabolism
chemical_list: C530104:CCND1 protein, human; D011993:Recombinant Fusion Proteins; D019938:Cyclin D1