Transcriptional activation of the proapoptotic bik gene by E2F proteins in cancer cells.
BH3-only proteins are required for execution of apoptotic cell death. We have found that one of these proteins, Bik, is strongly induced in cancer cells treated with chemotherapeutic agents. Furthermore, we showed that chemotherapy-induced expression of bik is independent of p53. Consistent with its pro-apoptotic activity, blockade of bik expression reduces the adriamycin-mediated apoptotic cell death. We also found that the bik gene is transcriptionally activated by E2F proteins. Consistently, adriamycin induces the E2F-bik pathway. In addition, E2Fs transactivate bik by a p53-independent mechanism. Thus, our data indicate that transcriptional regulation of bik contributes to the efficient apoptotic response to chemotherapeutic agents.
Real
Pedro J
PJ
Unidad de Genetica Molecular, Hospital Universitario Marques de Valdecilla, Av. Valdecilla s/n, 39008 Santander, Spain.
Sanz
Cristina
C
Gutierrez
Olga
O
Pipaon
Carlos
C
Zubiaga
Ana M
AM
Fernandez-Luna
Jose L
JL
D000970:Antineoplastic Agents / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects / Q000235:genetics* / Q000502:physiology; D051017:Apoptosis Regulatory Proteins / Q000235:genetics*; D001483:Base Sequence; D045744:Cell Line, Tumor; D004273:DNA, Neoplasm / Q000235:genetics; D004317:Doxorubicin / Q000494:pharmacology; D050684:E2F Transcription Factors / Q000378:metabolism*; D006801:Humans; D008565:Membrane Proteins / Q000235:genetics*; D024101:Mitochondrial Proteins; D009369:Neoplasms / Q000188:drug therapy / Q000235:genetics* / Q000378:metabolism / Q000473:pathology*; D011401:Promoter Regions, Genetic; D015533:Transcriptional Activation; D016159:Tumor Suppressor Protein p53 / Q000235:genetics / Q000378:metabolism
D000970:Antineoplastic Agents; D051017:Apoptosis Regulatory Proteins; C096820:BIK protein, human; D004273:DNA, Neoplasm; D050684:E2F Transcription Factors; D008565:Membrane Proteins; D024101:Mitochondrial Proteins; C495901:TP53 protein, human; D016159:Tumor Suppressor Protein p53; D004317:Doxorubicin