Potentiation of ceramide-induced apoptosis by p27kip1 overexpression.
The cyclin-dependent kinase inhibitor p27kip1 (p27) has been implicated in the regulation of cell cycle and apoptosis. Recently, we have demonstrated that ceramide induces apoptotic cell death associated with increase in the level of p27 in HL-60 cells. In the present study, we showed that overexpression of p27 increases ceramide-induced apoptotic cell death in HL-60 cells. Furthermore, overexpression of p27 accelerated DNA fragmentation, PARP cleavage and cytochrome c release induced by ceramide. In addition, ceramide induced Bax expression independent of p27. These findings indicate that enhanced effect on apoptosis by p27 is associated with mitochondrial signaling which involves cytochrome c release.
Kim
Hae Jong
HJ
Division of Biochemistry, College of Pharmacy, Chung-Ang University, Seoul 156-756, Korea.
Ghil
Kyung Chul
KC
Kim
Moo Sung
MS
Yeo
Seong Hyun
SH
Chun
Young Jin
YJ
Kim
Mie Young
MY
D017209:Apoptosis / Q000187:drug effects* / Q000502:physiology; D002352:Carrier Proteins / Q000096:biosynthesis* / Q000235:genetics*; D002518:Ceramides / Q000494:pharmacology*; D050760:Cyclin-Dependent Kinase Inhibitor p27; D005786:Gene Expression Regulation / Q000187:drug effects / Q000502:physiology; D018922:HL-60 Cells; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000235:genetics*
C436291:CDKN1B protein, human; D002352:Carrier Proteins; D002518:Ceramides; D047908:Intracellular Signaling Peptides and Proteins; C101954:N-caproylsphingosine; D050760:Cyclin-Dependent Kinase Inhibitor p27