Role for E2F in DNA damage-induced entry of cells into S phase.
Mammalian cells respond to ionizing radiation (IR) with transient cell cycle arrest and induction of apoptosis. Here we show that IR increases the expression of the E2F-1 transcription factor and the entry of cells into S phase. E2F-1 transactivation function is inhibited by cyclin A-kinase to ensure orderly progression through S phase. However, in contrast to proliferating cells, IR treatment results in down-regulation of cyclin A-kinase. Expression of a dominant negative form of the E2F heterodimeric partner DP-1 confirmed the involvement of E2F in IR-induced S-phase entry. These findings also support opposing signals involving the induction of E2F and the down-regulation of cyclin A-kinase in the IR response.
Huang
Y
Y
Division of Cancer Pharmacology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, Massachusetts 02115, USA.
Ishiko
T
T
Nakada
S
S
Utsugisawa
T
T
Kato
T
T
Yuan
Z M
ZM
D017209:Apoptosis; D002352:Carrier Proteins; D018797:Cell Cycle Proteins / Q000378:metabolism / Q000528:radiation effects*; D004247:DNA / Q000378:metabolism*; D004249:DNA Damage; D004268:DNA-Binding Proteins / Q000378:metabolism / Q000528:radiation effects*; D015536:Down-Regulation; D050684:E2F Transcription Factors; D050687:E2F1 Transcription Factor; D005434:Flow Cytometry; D016193:G1 Phase / Q000235:genetics; D018922:HL-60 Cells / Q000378:metabolism / Q000528:radiation effects; D006801:Humans; D011494:Protein Kinases / Q000378:metabolism / Q000528:radiation effects*; D012333:RNA, Messenger / Q000378:metabolism; D056465:Retinoblastoma-Binding Protein 1; D016196:S Phase / Q000235:genetics*; D050680:Transcription Factor DP1; D014157:Transcription Factors / Q000378:metabolism / Q000528:radiation effects*
D002352:Carrier Proteins; D018797:Cell Cycle Proteins; D004268:DNA-Binding Proteins; D050684:E2F Transcription Factors; D050687:E2F1 Transcription Factor; C493753:E2F1 protein, human; D012333:RNA, Messenger; D056465:Retinoblastoma-Binding Protein 1; C493735:TFDP1 protein, human; D050680:Transcription Factor DP1; D014157:Transcription Factors; D004247:DNA; D011494:Protein Kinases; C102333:histone H1 kinase