Roles of aurora‐A kinase in mitotic entry and G2 checkpoint in mammalian cells

Background: Various mitotic events are controlled by Cdc2‐cyclin B and other mitotic kinases. Aurora/Ipl1‐related mitotic kinases were proved to play key roles in mitotic progression in diverse lower organisms. Aurora‐A is a mammalian counterpart of aurora/Ipl1‐related kinases and is thought to be a...

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Veröffentlicht in:Genes to cells : devoted to molecular & cellular mechanisms 2002-11, Vol.7 (11), p.1173-1182
Hauptverfasser: Marumoto, Tomotoshi, Hirota, Toru, Morisaki, Tetsuro, Kunitoku, Naoko, Zhang, Dongwei, Ichikawa, Yasuko, Sasayama, Takashi, Kuninaka, Shinji, Mimori, Tatsuyuki, Tamaki, Norihiko, Kimura, Masashi, Okano, Yukio, Saya, Hideyuki
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container_end_page 1182
container_issue 11
container_start_page 1173
container_title Genes to cells : devoted to molecular & cellular mechanisms
container_volume 7
creator Marumoto, Tomotoshi
Hirota, Toru
Morisaki, Tetsuro
Kunitoku, Naoko
Zhang, Dongwei
Ichikawa, Yasuko
Sasayama, Takashi
Kuninaka, Shinji
Mimori, Tatsuyuki
Tamaki, Norihiko
Kimura, Masashi
Okano, Yukio
Saya, Hideyuki
description Background: Various mitotic events are controlled by Cdc2‐cyclin B and other mitotic kinases. Aurora/Ipl1‐related mitotic kinases were proved to play key roles in mitotic progression in diverse lower organisms. Aurora‐A is a mammalian counterpart of aurora/Ipl1‐related kinases and is thought to be a potential oncogene. However, the regulation of aurora‐A activation and the commitment of aurora‐A in the progression of G2‐M phase are largely unknown in mammalian cells. Results: We demonstrated that aurora‐A is activated depending on the activation of Cdc2‐cyclin B in mammalian cells. Since Cdc2‐cyclin B does not directly phosphorylate aurora‐A, indirect pathways such as the inhibition of PP1 by Cdc2‐cyclin B may act for the activation of aurora‐A kinase. Microinjection of anti‐aurora‐A antibodies into HeLa cells at late G2 phase caused a significant delay in mitotic entry. Furthermore, aurora‐A activation at G2‐M transition was inhibited by DNA damage, and the over‐expression of aurora‐A induced the abrogation of the DNA damage‐induced G2 checkpoint. Conclusions: Aurora‐A is activated downstream of Cdc2‐cyclin B and plays crucial roles in proper mitotic entry and G2 checkpoint control. Dysregulation of aurora‐A induces abnormal G2‐M transition in mammalian cells and may lead to chromosome instability, which results in the development and progression of malignant tumours.
doi_str_mv 10.1046/j.1365-2443.2002.00592.x
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Aurora/Ipl1‐related mitotic kinases were proved to play key roles in mitotic progression in diverse lower organisms. Aurora‐A is a mammalian counterpart of aurora/Ipl1‐related kinases and is thought to be a potential oncogene. However, the regulation of aurora‐A activation and the commitment of aurora‐A in the progression of G2‐M phase are largely unknown in mammalian cells. Results: We demonstrated that aurora‐A is activated depending on the activation of Cdc2‐cyclin B in mammalian cells. Since Cdc2‐cyclin B does not directly phosphorylate aurora‐A, indirect pathways such as the inhibition of PP1 by Cdc2‐cyclin B may act for the activation of aurora‐A kinase. Microinjection of anti‐aurora‐A antibodies into HeLa cells at late G2 phase caused a significant delay in mitotic entry. Furthermore, aurora‐A activation at G2‐M transition was inhibited by DNA damage, and the over‐expression of aurora‐A induced the abrogation of the DNA damage‐induced G2 checkpoint. Conclusions: Aurora‐A is activated downstream of Cdc2‐cyclin B and plays crucial roles in proper mitotic entry and G2 checkpoint control. 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Aurora/Ipl1‐related mitotic kinases were proved to play key roles in mitotic progression in diverse lower organisms. Aurora‐A is a mammalian counterpart of aurora/Ipl1‐related kinases and is thought to be a potential oncogene. However, the regulation of aurora‐A activation and the commitment of aurora‐A in the progression of G2‐M phase are largely unknown in mammalian cells. Results: We demonstrated that aurora‐A is activated depending on the activation of Cdc2‐cyclin B in mammalian cells. Since Cdc2‐cyclin B does not directly phosphorylate aurora‐A, indirect pathways such as the inhibition of PP1 by Cdc2‐cyclin B may act for the activation of aurora‐A kinase. Microinjection of anti‐aurora‐A antibodies into HeLa cells at late G2 phase caused a significant delay in mitotic entry. Furthermore, aurora‐A activation at G2‐M transition was inhibited by DNA damage, and the over‐expression of aurora‐A induced the abrogation of the DNA damage‐induced G2 checkpoint. Conclusions: Aurora‐A is activated downstream of Cdc2‐cyclin B and plays crucial roles in proper mitotic entry and G2 checkpoint control. Dysregulation of aurora‐A induces abnormal G2‐M transition in mammalian cells and may lead to chromosome instability, which results in the development and progression of malignant tumours.</description><subject>Animals</subject><subject>Antibodies - immunology</subject><subject>Aurora Kinase A</subject><subject>Aurora Kinases</subject><subject>Cell Cycle Proteins</subject><subject>Cyclin B1</subject><subject>Cyclin-Dependent Kinases - physiology</subject><subject>Enzyme Activation - physiology</subject><subject>G2 Phase - physiology</subject><subject>HeLa Cells</subject><subject>Humans</subject><subject>Mitosis - physiology</subject><subject>Phosphorylation</subject><subject>Protein Kinases - immunology</subject><subject>Protein Kinases - physiology</subject><subject>Protein-Serine-Threonine Kinases</subject><subject>Rats</subject><subject>Xenopus Proteins</subject><issn>1356-9597</issn><issn>1365-2443</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2002</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqNkM1Kw0AQxxdRbK2-guzJW-Ls7G4-wEspWoWCIvW8bJINbpuPmk2xvfkIPqNPYtIWPeppBuY3M39-hFAGPgMRXC98xgPpoRDcRwD0AWSM_uaIDH8Gx30vAy-WcTggZ84tABhHkKdkwJDHgJINydNzXRhH65zqdVM3-uvjc0yXttLOUFvR0rZ1a1NqqrbZUl1ldIo0fTXpclXbqt0huix1YXVFU1MU7pyc5Lpw5uJQR-Tl7nY-ufdmj9OHyXjmpSLg6GUJIGRRhkkYRjoSuUgwj0AnOU84CyHtgFyKLq4WsQzSAHSoBQOINIaAgo_I1f7uqqnf1sa1qrSuT6ArU6-dClFyCCT-CbJISkQJHRjtwbSpnWtMrlaNLXWzVQxUr10tVG9X9XZVr13ttKtNt3p5-LFOSpP9Lh48d8DNHni3hdn--7Caziddw78BUyuPrQ</recordid><startdate>200211</startdate><enddate>200211</enddate><creator>Marumoto, Tomotoshi</creator><creator>Hirota, Toru</creator><creator>Morisaki, Tetsuro</creator><creator>Kunitoku, Naoko</creator><creator>Zhang, Dongwei</creator><creator>Ichikawa, Yasuko</creator><creator>Sasayama, Takashi</creator><creator>Kuninaka, Shinji</creator><creator>Mimori, Tatsuyuki</creator><creator>Tamaki, Norihiko</creator><creator>Kimura, Masashi</creator><creator>Okano, Yukio</creator><creator>Saya, Hideyuki</creator><general>Blackwell Science Ltd</general><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>8FD</scope><scope>FR3</scope><scope>P64</scope><scope>RC3</scope><scope>7X8</scope></search><sort><creationdate>200211</creationdate><title>Roles of aurora‐A kinase in mitotic entry and G2 checkpoint in mammalian cells</title><author>Marumoto, Tomotoshi ; 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Aurora/Ipl1‐related mitotic kinases were proved to play key roles in mitotic progression in diverse lower organisms. Aurora‐A is a mammalian counterpart of aurora/Ipl1‐related kinases and is thought to be a potential oncogene. However, the regulation of aurora‐A activation and the commitment of aurora‐A in the progression of G2‐M phase are largely unknown in mammalian cells. Results: We demonstrated that aurora‐A is activated depending on the activation of Cdc2‐cyclin B in mammalian cells. Since Cdc2‐cyclin B does not directly phosphorylate aurora‐A, indirect pathways such as the inhibition of PP1 by Cdc2‐cyclin B may act for the activation of aurora‐A kinase. Microinjection of anti‐aurora‐A antibodies into HeLa cells at late G2 phase caused a significant delay in mitotic entry. Furthermore, aurora‐A activation at G2‐M transition was inhibited by DNA damage, and the over‐expression of aurora‐A induced the abrogation of the DNA damage‐induced G2 checkpoint. Conclusions: Aurora‐A is activated downstream of Cdc2‐cyclin B and plays crucial roles in proper mitotic entry and G2 checkpoint control. Dysregulation of aurora‐A induces abnormal G2‐M transition in mammalian cells and may lead to chromosome instability, which results in the development and progression of malignant tumours.</abstract><cop>Oxford, UK</cop><pub>Blackwell Science Ltd</pub><pmid>12390251</pmid><doi>10.1046/j.1365-2443.2002.00592.x</doi><tpages>10</tpages></addata></record>
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source Freely Accessible Japanese Titles - check A-Z of ejournals; Wiley-Blackwell Journals; MEDLINE; Wiley Free Archive; EZB Electronic Journals Library
subjects Animals
Antibodies - immunology
Aurora Kinase A
Aurora Kinases
Cell Cycle Proteins
Cyclin B1
Cyclin-Dependent Kinases - physiology
Enzyme Activation - physiology
G2 Phase - physiology
HeLa Cells
Humans
Mitosis - physiology
Phosphorylation
Protein Kinases - immunology
Protein Kinases - physiology
Protein-Serine-Threonine Kinases
Rats
Xenopus Proteins
title Roles of aurora‐A kinase in mitotic entry and G2 checkpoint in mammalian cells
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