Activation of cyclin-dependent kinase 2 (Cdk2) in growth-stimulated rat astrocytes: Geranylgeranylated Rho small GTPase(s) are essential for the induction of cyclin E gene expression

Tomoaki Tanaka, Ichiro Tatsuno, Yoshihiko Noguchi, Daigaku Uchida, Toru Oeda, Shuh Narumiya, Tatsuji Yasuda, Hideaki Higashi, Masatoshi Kitagawa, Keiichi Nakayama, Yasushi Saito, Aizan Hirai

研究成果: ジャーナルへの寄稿記事

35 引用 (Scopus)

抄録

The role of the mevalonate cascade in the control of cell cycle progression in astrocytes has been investigated. Serum stimulation of rat astrocytes in primary culture induces the expression of cyclin E followed by the activation of cyclin-dependent kinase 2 (Cdk2) during G1/S transition. The expression of p27(kip1), cyclin D1, and the activities of Cdk4 and Cdk- activating kinase (CAK), composed of Cdk7 and cyclin H, were not affected. Serum did, however, stimulate the expression of 3-hydroxy-3-methylglutaryl- CoA (HMG-CoA) reductase mRNA at mid-G1 phase. Moreover, an inhibitor of HMG- CoA reductase, pravastatin, reduced cyclin E expression and Cdk2 activation and caused G1 arrest in the astrocytes. In contrast, mevalonate and its metabolite, geranylgeranylpyrophosphate (GGPP) but not farnesylpyrophosphate (FPP), reversed the inhibitory effects of pravastatin on cyclin E expression and Cdk2 activation and allowed G1/S transition. Rho small GTPase(s) were geranylgeranylated and translocated to membranes in the presence of GGPP during G1/S transition. The effect of GGPP on cyclin E expression was abolished by botulinum C3 exoenzyme, which specifically inactivates Rho. These data indicate that geranylgeranylated Rho small GTPase(s) are essential for the induction of cyclin E expression, Cdk2 activation, and G1/S transition in rat astrocytes.

元の言語英語
ページ(範囲)26772-26778
ページ数7
ジャーナルJournal of Biological Chemistry
273
発行部数41
DOI
出版物ステータス出版済み - 10 9 1998

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Cyclin-Dependent Kinase 2
Cyclin E
rho GTP-Binding Proteins
Monomeric GTP-Binding Proteins
Gene expression
Astrocytes
Rats
Chemical activation
Gene Expression
Growth
Pravastatin
Mevalonic Acid
Cyclin H
Hydroxymethylglutaryl CoA Reductases
Hydroxymethylglutaryl-CoA Reductase Inhibitors
Cyclin D1
G1 Phase
Metabolites
Cell Cycle Checkpoints
Serum

All Science Journal Classification (ASJC) codes

  • Biochemistry
  • Molecular Biology
  • Cell Biology

これを引用

Activation of cyclin-dependent kinase 2 (Cdk2) in growth-stimulated rat astrocytes : Geranylgeranylated Rho small GTPase(s) are essential for the induction of cyclin E gene expression. / Tanaka, Tomoaki; Tatsuno, Ichiro; Noguchi, Yoshihiko; Uchida, Daigaku; Oeda, Toru; Narumiya, Shuh; Yasuda, Tatsuji; Higashi, Hideaki; Kitagawa, Masatoshi; Nakayama, Keiichi; Saito, Yasushi; Hirai, Aizan.

:: Journal of Biological Chemistry, 巻 273, 番号 41, 09.10.1998, p. 26772-26778.

研究成果: ジャーナルへの寄稿記事

Tanaka, Tomoaki ; Tatsuno, Ichiro ; Noguchi, Yoshihiko ; Uchida, Daigaku ; Oeda, Toru ; Narumiya, Shuh ; Yasuda, Tatsuji ; Higashi, Hideaki ; Kitagawa, Masatoshi ; Nakayama, Keiichi ; Saito, Yasushi ; Hirai, Aizan. / Activation of cyclin-dependent kinase 2 (Cdk2) in growth-stimulated rat astrocytes : Geranylgeranylated Rho small GTPase(s) are essential for the induction of cyclin E gene expression. :: Journal of Biological Chemistry. 1998 ; 巻 273, 番号 41. pp. 26772-26778.
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abstract = "The role of the mevalonate cascade in the control of cell cycle progression in astrocytes has been investigated. Serum stimulation of rat astrocytes in primary culture induces the expression of cyclin E followed by the activation of cyclin-dependent kinase 2 (Cdk2) during G1/S transition. The expression of p27(kip1), cyclin D1, and the activities of Cdk4 and Cdk- activating kinase (CAK), composed of Cdk7 and cyclin H, were not affected. Serum did, however, stimulate the expression of 3-hydroxy-3-methylglutaryl- CoA (HMG-CoA) reductase mRNA at mid-G1 phase. Moreover, an inhibitor of HMG- CoA reductase, pravastatin, reduced cyclin E expression and Cdk2 activation and caused G1 arrest in the astrocytes. In contrast, mevalonate and its metabolite, geranylgeranylpyrophosphate (GGPP) but not farnesylpyrophosphate (FPP), reversed the inhibitory effects of pravastatin on cyclin E expression and Cdk2 activation and allowed G1/S transition. Rho small GTPase(s) were geranylgeranylated and translocated to membranes in the presence of GGPP during G1/S transition. The effect of GGPP on cyclin E expression was abolished by botulinum C3 exoenzyme, which specifically inactivates Rho. These data indicate that geranylgeranylated Rho small GTPase(s) are essential for the induction of cyclin E expression, Cdk2 activation, and G1/S transition in rat astrocytes.",
author = "Tomoaki Tanaka and Ichiro Tatsuno and Yoshihiko Noguchi and Daigaku Uchida and Toru Oeda and Shuh Narumiya and Tatsuji Yasuda and Hideaki Higashi and Masatoshi Kitagawa and Keiichi Nakayama and Yasushi Saito and Aizan Hirai",
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T1 - Activation of cyclin-dependent kinase 2 (Cdk2) in growth-stimulated rat astrocytes

T2 - Geranylgeranylated Rho small GTPase(s) are essential for the induction of cyclin E gene expression

AU - Tanaka, Tomoaki

AU - Tatsuno, Ichiro

AU - Noguchi, Yoshihiko

AU - Uchida, Daigaku

AU - Oeda, Toru

AU - Narumiya, Shuh

AU - Yasuda, Tatsuji

AU - Higashi, Hideaki

AU - Kitagawa, Masatoshi

AU - Nakayama, Keiichi

AU - Saito, Yasushi

AU - Hirai, Aizan

PY - 1998/10/9

Y1 - 1998/10/9

N2 - The role of the mevalonate cascade in the control of cell cycle progression in astrocytes has been investigated. Serum stimulation of rat astrocytes in primary culture induces the expression of cyclin E followed by the activation of cyclin-dependent kinase 2 (Cdk2) during G1/S transition. The expression of p27(kip1), cyclin D1, and the activities of Cdk4 and Cdk- activating kinase (CAK), composed of Cdk7 and cyclin H, were not affected. Serum did, however, stimulate the expression of 3-hydroxy-3-methylglutaryl- CoA (HMG-CoA) reductase mRNA at mid-G1 phase. Moreover, an inhibitor of HMG- CoA reductase, pravastatin, reduced cyclin E expression and Cdk2 activation and caused G1 arrest in the astrocytes. In contrast, mevalonate and its metabolite, geranylgeranylpyrophosphate (GGPP) but not farnesylpyrophosphate (FPP), reversed the inhibitory effects of pravastatin on cyclin E expression and Cdk2 activation and allowed G1/S transition. Rho small GTPase(s) were geranylgeranylated and translocated to membranes in the presence of GGPP during G1/S transition. The effect of GGPP on cyclin E expression was abolished by botulinum C3 exoenzyme, which specifically inactivates Rho. These data indicate that geranylgeranylated Rho small GTPase(s) are essential for the induction of cyclin E expression, Cdk2 activation, and G1/S transition in rat astrocytes.

AB - The role of the mevalonate cascade in the control of cell cycle progression in astrocytes has been investigated. Serum stimulation of rat astrocytes in primary culture induces the expression of cyclin E followed by the activation of cyclin-dependent kinase 2 (Cdk2) during G1/S transition. The expression of p27(kip1), cyclin D1, and the activities of Cdk4 and Cdk- activating kinase (CAK), composed of Cdk7 and cyclin H, were not affected. Serum did, however, stimulate the expression of 3-hydroxy-3-methylglutaryl- CoA (HMG-CoA) reductase mRNA at mid-G1 phase. Moreover, an inhibitor of HMG- CoA reductase, pravastatin, reduced cyclin E expression and Cdk2 activation and caused G1 arrest in the astrocytes. In contrast, mevalonate and its metabolite, geranylgeranylpyrophosphate (GGPP) but not farnesylpyrophosphate (FPP), reversed the inhibitory effects of pravastatin on cyclin E expression and Cdk2 activation and allowed G1/S transition. Rho small GTPase(s) were geranylgeranylated and translocated to membranes in the presence of GGPP during G1/S transition. The effect of GGPP on cyclin E expression was abolished by botulinum C3 exoenzyme, which specifically inactivates Rho. These data indicate that geranylgeranylated Rho small GTPase(s) are essential for the induction of cyclin E expression, Cdk2 activation, and G1/S transition in rat astrocytes.

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