How does chemotherapy induce apoptosis?
Inhibition of any vital metabolic process can lead to stress responses, including apoptosis. For some therapies, the detection and signal transduction pathways have been elucidated. Damage to DNA caused by ionizing radiation or drugs, for example, can lead to stabilization of p53 (Giaccia and Kastan, 1998; Abraham, 2001) and consequent transcriptional activation of genes encoding a number of polypeptides, including Bax (Miyashita and Reed, 1995), Apaf-1 (Fortin et al., 2001; Kannan et al., 2001; Robles et al., 2001), the BH3-only polypeptides Noxa and PUMA (Oda et al., 2000a; Yu et al., 2001), and p53AIP1 (Oda et al., 2000b). Each of these polypeptides can potentially activate the Bcl-2-inhibitable pathway. Because of the involvement of other transcriptional activators and repressors in expression of these polypeptides, not all of these polypeptides are regulated to the same extent by p53 in all model systems. The role of Bax transcription in p53-induced death, for example, has been qu
