Genotoxic stress induces expression of E2F4, leading to its association with p130 in prostate carcinoma cells.
The retinoblastoma (pRb), p107, and p130 pocket proteins bind to the E2F transcription factors to control gene expression. E2F4 protein levels increased and accumulated in the nuclei of prostate carcinoma cells subjected to ionizing radiation (IR). The IR-induced increase of E2F4 levels led to an increase in E2F4 binding to p130 but had no effect on E2F4/p107 or E2F5/p130 complexes. The increase in E2F4/p130 association after IR was observed in prostate carcinoma cells regardless of their sensitivity to androgens, but not in breast carcinoma cells. E2F4/p130 complex formation was dependent on dissociation of p130 from cyclin-dependent kinase 2 and p130 dephosphorylation. Disruption of E2F4 through small interfering RNA prevented p130/E2F4 complex formation and sensitized cells to IR-induced apoptosis, leading to caspase-3 activation, cleavage of its substrate, poly(ADP-ribose) polymerase, and nuclear condensation. The E2F4/p130 pocket protein complex emerges as a new target of radiation in prostate carcinoma cells.
DuPree
Erica L
EL
Department of Cancer Biology, Lerner Research Institute, Cleveland Clinic Foundation, Cleveland, Ohio 44195, USA.
Mazumder
Suparna
S
Almasan
Alexandru
A
D017209:Apoptosis / Q000235:genetics / Q000528:radiation effects; D001943:Breast Neoplasms / Q000235:genetics / Q000378:metabolism / Q000532:radiotherapy; D045744:Cell Line, Tumor; D004268:DNA-Binding Proteins / Q000096:biosynthesis* / Q000235:genetics / Q000378:metabolism / Q000528:radiation effects; D015536:Down-Regulation / Q000235:genetics / Q000528:radiation effects; D050704:E2F4 Transcription Factor; D015972:Gene Expression Regulation, Neoplastic / Q000235:genetics* / Q000528:radiation effects; D006801:Humans; D008297:Male; D009376:Neoplasms, Hormone-Dependent / Q000235:genetics / Q000378:metabolism / Q000532:radiotherapy; D011471:Prostatic Neoplasms / Q000235:genetics* / Q000378:metabolism* / Q000532:radiotherapy; D014176:Protein Biosynthesis; D011506:Proteins / Q000235:genetics / Q000378:metabolism / Q000528:radiation effects; D034741:RNA, Small Interfering / Q000235:genetics; D050717:Retinoblastoma-Like Protein p130; D014157:Transcription Factors / Q000096:biosynthesis* / Q000235:genetics / Q000378:metabolism / Q000528:radiation effects; D014162:Transfection
D004268:DNA-Binding Proteins; D050704:E2F4 Transcription Factor; D011506:Proteins; C493837:RBL2 protein, human; D034741:RNA, Small Interfering; D050717:Retinoblastoma-Like Protein p130; D014157:Transcription Factors