Distinct patterns of cleavage and translocation of cell cycle control proteins in CD95-induced and p53-induced apoptosis.
Apoptotic cell death induced by p53 occurs at a late G1 cell cycle checkpoint termed the restriction (R) point, and it has been proposed that p53-induced apoptosis causes upregulation of CD95. However, as cells with defective in CD95 signaling pathway are still sensitive to p53-induced apoptosis, CD95 cannot be the sole factor resulting in apoptosis. In addition, unlike p53-induced apoptosis, the relationship between CD95-mediated apoptosis and the cell cycle is not clearly understood. It would therefore be worth investigating whether CD95-mediated cell death is pertinent with p53-induced apoptosis in view of cell cycle related molecules. In this report, biochemical analysis showed that etoposide-induced apoptosis caused the induction and the nuclear translocation of effector molecules involved in G1 cell cycle checkpoint. However, there was no such translocation in the case of CD95-mediated death. Thus, although both types of apoptosis involved caspase activation, the cell cycle related proteins responded differently. This argues against the idea that p53-induced apoptosis occurs through the induction of CD95/CD95L expression.
Park
Weon Seo
WS
Department of Pathology, Kangwon National University College of Medicine, Korea.
Jung
Kyeong Cheon
KC
Chung
Doo Hyun
DH
Nam
Woo-Dong
WD
Choi
Won Jin
WJ
Bae
Youngmee
Y
D021581:Active Transport, Cell Nucleus; D017209:Apoptosis; D002453:Cell Cycle; D002467:Cell Nucleus / Q000378:metabolism; D018920:Coculture Techniques; D004305:Dose-Response Relationship, Drug; D015536:Down-Regulation; D005047:Etoposide / Q000494:pharmacology; D005434:Flow Cytometry; D006801:Humans; D015151:Immunoblotting; D019169:Jurkat Cells; D019384:Nucleic Acid Synthesis Inhibitors / Q000494:pharmacology; D011485:Protein Binding; D021381:Protein Transport; D015398:Signal Transduction; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism*; D015854:Up-Regulation; D019014:fas Receptor / Q000378:metabolism*
D019384:Nucleic Acid Synthesis Inhibitors; D016159:Tumor Suppressor Protein p53; D019014:fas Receptor; D005047:Etoposide