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

David A. Bennin, Aruni S. Arachchige Don, Tiffany Brake, Jennifer L. McKenzie, Heidi Rosenbaum, Linette Ortiz, Anna De Paoli-Roach, Mary C. Horne

Research output: Contribution to journalArticle

158 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)27449-27467
Number of pages19
JournalJournal of Biological Chemistry
Volume277
Issue number30
DOIs
StatePublished - Jul 26 2002

Fingerprint

Cyclin G2
Protein Phosphatase 2
G1 Phase
Cell Cycle Checkpoints
Aberrations
S Phase
Cells
Cyclin G1
Cell Cycle
Phosphoprotein Phosphatases
Cyclin I
Detergents
Okadaic Acid
Cyclins

ASJC Scopus subject areas

  • Biochemistry

Cite this

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. / Bennin, David A.; Arachchige Don, Aruni S.; Brake, Tiffany; McKenzie, Jennifer L.; Rosenbaum, Heidi; Ortiz, Linette; De Paoli-Roach, Anna; Horne, Mary C.

In: Journal of Biological Chemistry, Vol. 277, No. 30, 26.07.2002, p. 27449-27467.

Research output: Contribution to journalArticle

Bennin, David A. ; Arachchige Don, Aruni S. ; Brake, Tiffany ; McKenzie, Jennifer L. ; Rosenbaum, Heidi ; Ortiz, Linette ; De Paoli-Roach, Anna ; Horne, Mary C. / 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. In: Journal of Biological Chemistry. 2002 ; Vol. 277, No. 30. pp. 27449-27467.
@article{abe9653fcb9f4da7992757e0f233bb99,
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.",
author = "Bennin, {David A.} and {Arachchige Don}, {Aruni S.} and Tiffany Brake and McKenzie, {Jennifer L.} and Heidi Rosenbaum and Linette Ortiz and {De Paoli-Roach}, Anna and Horne, {Mary C.}",
year = "2002",
month = "7",
day = "26",
doi = "10.1074/jbc.M111693200",
language = "English",
volume = "277",
pages = "27449--27467",
journal = "Journal of Biological Chemistry",
issn = "0021-9258",
publisher = "American Society for Biochemistry and Molecular Biology Inc.",
number = "30",

}

TY - JOUR

T1 - 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

AU - Bennin, David A.

AU - Arachchige Don, Aruni S.

AU - Brake, Tiffany

AU - McKenzie, Jennifer L.

AU - Rosenbaum, Heidi

AU - Ortiz, Linette

AU - De Paoli-Roach, Anna

AU - Horne, Mary C.

PY - 2002/7/26

Y1 - 2002/7/26

N2 - 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.

AB - 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.

UR - http://www.scopus.com/inward/record.url?scp=0037178863&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0037178863&partnerID=8YFLogxK

U2 - 10.1074/jbc.M111693200

DO - 10.1074/jbc.M111693200

M3 - Article

C2 - 11956189

AN - SCOPUS:0037178863

VL - 277

SP - 27449

EP - 27467

JO - Journal of Biological Chemistry

JF - Journal of Biological Chemistry

SN - 0021-9258

IS - 30

ER -