Overexpression of cdk4/cyclin D1 induces apoptosis in PC12 cells in the presence of trophic support

Kazuhiro Katayama; Yoh Dobashi; Masatoshi Kitagawa; Soichiro Kamekura; Masataka Kawai; Yuichi Kadoya; Toru Kameya

doi:10.1016/S0014-5793(01)03200-8

Overexpression of cdk4/cyclin D1 induces apoptosis in PC12 cells in the presence of trophic support

Kazuhiro Katayama, Yoh Dobashi, Masatoshi Kitagawa, Soichiro Kamekura, Masataka Kawai, Yuichi Kadoya, Toru Kameya

School of Pharmacy

Research output: Contribution to journal › Article › peer-review

18 Citations (Scopus)

Abstract

The induction of apoptosis by cell cycle regulator molecules under conditions optimal for exponential growth was examined in rat pheochromocytoma PC12 cells by overexpression of cyclins and cyclin-dependent kinases (cdks). By flow cytometry and by immunofluorescence, only cells overexpressing cdk4 or cyclin D1 underwent apoptosis, which was not associated with G1-arrest. Cdk4 kinase activity was significantly higher in cdk4-, or cyclin D1-expressing cells. Furthermore, induction of apoptosis by cdk4 was abrogated by co-transfection of p16^INK4, or dominant negative cdk4. These results suggest that upregulation of cdk4 kinase activity is a primary and critical mediator of apoptosis in PC12 cells under physiological conditions.

Original language	English
Pages (from-to)	382-388
Number of pages	7
Journal	FEBS Letters
Volume	509
Issue number	3
DOIs	https://doi.org/10.1016/S0014-5793(01)03200-8
Publication status	Published - 2001 Dec 14

Keywords

Apoptosis
Cdk inhibitor
Cdk4
Cyclin D1
Dominant negative cdk4
PC12 cell

ASJC Scopus subject areas

Biophysics
Structural Biology
Biochemistry
Molecular Biology
Genetics
Cell Biology

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@article{118c258cae8c4b68b6f3e901cdb669ab,

title = "Overexpression of cdk4/cyclin D1 induces apoptosis in PC12 cells in the presence of trophic support",

abstract = "The induction of apoptosis by cell cycle regulator molecules under conditions optimal for exponential growth was examined in rat pheochromocytoma PC12 cells by overexpression of cyclins and cyclin-dependent kinases (cdks). By flow cytometry and by immunofluorescence, only cells overexpressing cdk4 or cyclin D1 underwent apoptosis, which was not associated with G1-arrest. Cdk4 kinase activity was significantly higher in cdk4-, or cyclin D1-expressing cells. Furthermore, induction of apoptosis by cdk4 was abrogated by co-transfection of p16INK4, or dominant negative cdk4. These results suggest that upregulation of cdk4 kinase activity is a primary and critical mediator of apoptosis in PC12 cells under physiological conditions.",

keywords = "Apoptosis, Cdk inhibitor, Cdk4, Cyclin D1, Dominant negative cdk4, PC12 cell",

author = "Kazuhiro Katayama and Yoh Dobashi and Masatoshi Kitagawa and Soichiro Kamekura and Masataka Kawai and Yuichi Kadoya and Toru Kameya",

note = "Funding Information: This work was supported in part by a Grant-in-Aid for Scientific Research, No. 11670191 from the Ministry of Education, Science and Culture in Japan and by Kitasato University Medical Science Research Project 2005.",

year = "2001",

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doi = "10.1016/S0014-5793(01)03200-8",

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T1 - Overexpression of cdk4/cyclin D1 induces apoptosis in PC12 cells in the presence of trophic support

AU - Katayama, Kazuhiro

AU - Dobashi, Yoh

AU - Kitagawa, Masatoshi

AU - Kamekura, Soichiro

AU - Kawai, Masataka

AU - Kadoya, Yuichi

AU - Kameya, Toru

N1 - Funding Information: This work was supported in part by a Grant-in-Aid for Scientific Research, No. 11670191 from the Ministry of Education, Science and Culture in Japan and by Kitasato University Medical Science Research Project 2005.

PY - 2001/12/14

Y1 - 2001/12/14

N2 - The induction of apoptosis by cell cycle regulator molecules under conditions optimal for exponential growth was examined in rat pheochromocytoma PC12 cells by overexpression of cyclins and cyclin-dependent kinases (cdks). By flow cytometry and by immunofluorescence, only cells overexpressing cdk4 or cyclin D1 underwent apoptosis, which was not associated with G1-arrest. Cdk4 kinase activity was significantly higher in cdk4-, or cyclin D1-expressing cells. Furthermore, induction of apoptosis by cdk4 was abrogated by co-transfection of p16INK4, or dominant negative cdk4. These results suggest that upregulation of cdk4 kinase activity is a primary and critical mediator of apoptosis in PC12 cells under physiological conditions.

AB - The induction of apoptosis by cell cycle regulator molecules under conditions optimal for exponential growth was examined in rat pheochromocytoma PC12 cells by overexpression of cyclins and cyclin-dependent kinases (cdks). By flow cytometry and by immunofluorescence, only cells overexpressing cdk4 or cyclin D1 underwent apoptosis, which was not associated with G1-arrest. Cdk4 kinase activity was significantly higher in cdk4-, or cyclin D1-expressing cells. Furthermore, induction of apoptosis by cdk4 was abrogated by co-transfection of p16INK4, or dominant negative cdk4. These results suggest that upregulation of cdk4 kinase activity is a primary and critical mediator of apoptosis in PC12 cells under physiological conditions.

KW - Apoptosis

KW - Cdk inhibitor

KW - Cdk4

KW - Cyclin D1

KW - Dominant negative cdk4

KW - PC12 cell

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