title: Cyclin G2 associates with protein phosphatase 2A catalytic and regulatory B' subunits in active complexes and induces nuclear aberrations and a G1/S phase cell cycle arrest.
abstract: Cyclin G2, together with cyclin G1 and cyclin I, defines a novel cyclin family expressed in terminally differentiated tissues including brain and muscle. Cyclin G2 expression is up-regulated as cells undergo cell cycle arrest or apoptosis in response to inhibitory stimuli independent of p53 (Horne, M., Donaldson, K., Goolsby, G., Tran, D., Mulheisen, M., Hell, J. and Wahl, A. (1997) J. Biol. Chem. 272, 12650-12661). We tested the hypothesis that cyclin G2 may be a negative regulator of cell cycle progression and found that ectopic expression of cyclin G2 induces the formation of aberrant nuclei and cell cycle arrest in HEK293 and Chinese hamster ovary cells. Cyclin G2 is primarily partitioned to a detergent-resistant compartment, suggesting an association with cytoskeletal elements. We determined that cyclin G2 and its homolog cyclin G1 directly interact with the catalytic subunit of protein phosphatase 2A (PP2A). An okadaic acid-sensitive (<2 nm) phosphatase activity coprecipitates with endogenous and ectopic cyclin G2. We found that cyclin G2 also associates with various PP2A B' regulatory subunits, as previously shown for cyclin G1. The PP2A/A subunit is not detectable in cyclin G2-PP2A-B'-C complexes. Notably, cyclin G2 colocalizes with both PP2A/C and B' subunits in detergent-resistant cellular compartments, suggesting that these complexes form in living cells. The ability of cyclin G2 to inhibit cell cycle progression correlates with its ability to bind PP2A/B' and C subunits. Together, our findings suggest that cyclin G2-PP2A complexes inhibit cell cycle progression.
authors.affiliation: Department of Pharmacology, University of Wisconsin, Madison, WI 53706-1532, USA.
authors.forename: David A
authors.initials: DA
authors.lastname: Bennin
authors.forename: Aruni S Arachchige
authors.initials: AS
authors.lastname: Don
authors.forename: Tiffany
authors.initials: T
authors.lastname: Brake
authors.forename: Jennifer L
authors.initials: JL
authors.lastname: McKenzie
authors.forename: Heidi
authors.initials: H
authors.lastname: Rosenbaum
authors.forename: Linette
authors.initials: L
authors.lastname: Ortiz
authors.forename: Anna A
authors.initials: AA
authors.lastname: DePaoli-Roach
authors.forename: Mary C
authors.initials: MC
authors.lastname: Horne
mesh_terms: D020816:Amino Acid Motifs; D000818:Animals; D001973:Bromodeoxyuridine / Q000494:pharmacology; D016466:CHO Cells; D020134:Catalytic Domain; D002453:Cell Cycle; D002454:Cell Differentiation; D002460:Cell Line; D002467:Cell Nucleus / Q000378:metabolism; D002469:Cell Separation; D002845:Chromatography; D006224:Cricetinae; D056767:Cyclin G2; D016213:Cyclins / Q000378:metabolism*; D003902:Detergents / Q000494:pharmacology; D005347:Fibroblasts / Q000378:metabolism; D005434:Flow Cytometry; D016193:G1 Phase; D005982:Glutathione Transferase / Q000378:metabolism; D006801:Humans; D008856:Microscopy, Fluorescence; D008938:Mitosis; D010749:Phosphoprotein Phosphatases / Q000737:chemistry* / Q000378:metabolism; D010766:Phosphorylation; D011233:Precipitin Tests; D011485:Protein Binding; D054648:Protein Phosphatase 2; D017434:Protein Structure, Tertiary; D011993:Recombinant Fusion Proteins / Q000378:metabolism; D016196:S Phase; D014162:Transfection; D015854:Up-Regulation
chemical_list: C101593:CCNG2 protein, human; D056767:Cyclin G2; D016213:Cyclins; D003902:Detergents; D011993:Recombinant Fusion Proteins; D005982:Glutathione Transferase; D010749:Phosphoprotein Phosphatases; D054648:Protein Phosphatase 2; D001973:Bromodeoxyuridine