TY - JOUR
T1 - A novel apoptotic cascade mediated by CDK4 in rat pheochromocytoma PC12 cells
AU - Dobashi, Yoh
AU - Shoji, Mitsuhiko
AU - Noguchi, Takashi
AU - Kondo, Eisaku
AU - Katayama, Kazuhiro
AU - Kameya, Toru
N1 - Funding Information:
This work was supported by Grants-in-Aid for Scientific Research, No. 09770130, from the Ministry of Education, Science, and Culture, in Japan and by Mitsui Life Social Welfare Foundation Research Grant.
PY - 1999/7/14
Y1 - 1999/7/14
N2 - Apoptosis induced by serum withdrawal in pheochromocytoma PC12 cells is promoted by overexpression of cyclin-dependent kinase 4 (CDK4). We compared CDK4-promoted apoptosis with that induced by serum withdrawal alone in PC12 cells. Protein synthesis inhibitors did not prevent apoptosis in parental cells, but prevented the promotion of apoptosis by CDK4 overexpression. Nerve growth factor, basic-fibroblast growth factor, and Bcl-2 proteins protected both parental and CDK4-overexpressing cells from apoptosis. However, insulin-like growth factor-I and Bcl-X(L) protein only partially inhibited apoptosis in the CDK4-overexpressing cells. Bcl-2 or Bcl-X(L) had no significant effect on CDK4 kinase activity in both cell lines. These results suggest a novel CDK4-mediated apoptotic cascade which is normally restrained, but which is activated by CDK4 overexpression. This apoptotic cascade should eventually converge with the cascade induced by serum withdrawal in normal PC12 cells. We discuss the interactions among these apoptotic cascades and the points where anti-apoptotic agents act.
AB - Apoptosis induced by serum withdrawal in pheochromocytoma PC12 cells is promoted by overexpression of cyclin-dependent kinase 4 (CDK4). We compared CDK4-promoted apoptosis with that induced by serum withdrawal alone in PC12 cells. Protein synthesis inhibitors did not prevent apoptosis in parental cells, but prevented the promotion of apoptosis by CDK4 overexpression. Nerve growth factor, basic-fibroblast growth factor, and Bcl-2 proteins protected both parental and CDK4-overexpressing cells from apoptosis. However, insulin-like growth factor-I and Bcl-X(L) protein only partially inhibited apoptosis in the CDK4-overexpressing cells. Bcl-2 or Bcl-X(L) had no significant effect on CDK4 kinase activity in both cell lines. These results suggest a novel CDK4-mediated apoptotic cascade which is normally restrained, but which is activated by CDK4 overexpression. This apoptotic cascade should eventually converge with the cascade induced by serum withdrawal in normal PC12 cells. We discuss the interactions among these apoptotic cascades and the points where anti-apoptotic agents act.
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U2 - 10.1006/bbrc.1999.0983
DO - 10.1006/bbrc.1999.0983
M3 - Article
C2 - 10403846
AN - SCOPUS:0033554035
SN - 0006-291X
VL - 260
SP - 806
EP - 812
JO - Biochemical and Biophysical Research Communications
JF - Biochemical and Biophysical Research Communications
IS - 3
ER -