Inducing cancer cell death by targeting transcription factors.
We review the biological significance of transcription factors such as p53, Myc, E2F family and AP-1 (Jun/Fos) in anticancer drug-induced apoptosis. It is likely that the functional role of these transcription factors is complex in response to DNA damage depending on cancer cell type. Regulation of apoptosis following DNA damage is mediated by cell cycle arrest for DNA repair and subsequent signal transduction pathways leading to apoptosis, which is associated with mitochondrial dysfunction. Activation of transcription factors following anticancer drugs is located upstream of signal transduction pathways, thereby the downstream pathway is promoted, which is connected to activation or suppression of apoptosis-related proteins. Switching on apoptotic signals by anticancer drugs is amplified in mitochondria by releasing cytochrome from the ion channel to activate the caspase cascade, which is regulated by Bcl-2 families in the central gate for drug-induced apoptosis. Activation of transcription factors targeting downstream genes, some of which are apoptosis-related genes, can play a critical role in promoting apoptosis following treatment with anticancer drugs. The strategy of identification of downstream target proteins or transcription factors involved in apoptosis will be necessary for the development of an effective transcription factor-targeted chemotherapy for cancer.
Kim
Ryungsa
R
Department of Surgical Oncology, Research Institute for Radiation Biology and Medicine, Hiroshima University, Hiroshima, Japan. rkim@hiroshima-u.ac.jp
Tanabe
Kazuaki
K
Emi
Manabu
M
Uchida
Yoko
Y
Inoue
Hideki
H
Toge
Tetsuya
T
D000818:Animals; D017209:Apoptosis / Q000187:drug effects / Q000502:physiology; D016923:Cell Death / Q000187:drug effects / Q000502:physiology; D016503:Drug Delivery Systems / Q000379:methods*; D006801:Humans; D009369:Neoplasms / Q000378:metabolism* / Q000473:pathology*; D014157:Transcription Factors / Q000378:metabolism*
D014157:Transcription Factors