MOLECULAR BASIS OF CELL AND DEVELOPMENTAL BIOLOGY
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*

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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.

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Published, JBC Papers in Press, April 15, 2002, DOI 10.1074/jbc.M111693200

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This work was supported by National Institutes of Health Grant R01GM56900 and American Heart Association Grant 9806386X (to M. C. H.).The costs of publication of this article were defrayed in part by the payment of page charges. The article must therefore be hereby marked “advertisement” in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.