c-Jun induces apoptosis of starved BM2 monoblasts by activating cyclin A-CDK2.
c-Jun is one of the major components of the activating protein-1 (AP-1), the transcription factor that participates in regulation of proliferation, differentiation, and apoptosis. In this study, we explored functional interactions of the c-Jun protein with several regulators of the G1/S transition in serum-deprived v-myb-transformed chicken monoblasts BM2. We show that the c-Jun protein induces expression of cyclin A, thus up-regulating activity of cyclin A-associated cyclin-dependent kinase 2 (CDK2), and causing massive programmed cell death of starved BM2cJUN cells. Specific inhibition of CDK2 suppresses frequency of apoptosis of BM2cJUN cells. We conclude that up-regulation of cyclin A expression and CDK2 activity can represent important link between the c-Jun protein, cell cycle machinery, and programmed cell death pathway in leukemic cells.
Vanhara
Petr
P
Institute of Experimental Biology, Faculty of Science, Masaryk University, Brno, Czech Republic.
Bryja
Vítezslav
V
Horváth
Viktor
V
Kozubík
Alois
A
Hampl
Ales
A
Smarda
Jan
J
D000818:Animals; D017209:Apoptosis; D002460:Cell Line; D002471:Cell Transformation, Neoplastic / Q000378:metabolism*; D002645:Chickens; D016895:Culture Media, Serum-Free; D051357:Cyclin-Dependent Kinase 2 / Q000378:metabolism*; D004789:Enzyme Activation; D007948:Leukemia, Monocytic, Acute / Q000378:metabolism*; D018384:Oxidative Stress; D016755:Proto-Oncogene Proteins c-jun / Q000378:metabolism*; D015398:Signal Transduction
D016895:Culture Media, Serum-Free; D016755:Proto-Oncogene Proteins c-jun; D051357:Cyclin-Dependent Kinase 2