E2F1 transcription is induced by genotoxic stress through ATM/ATR activation.
E2F1, a member of the E2F family of transcription factors, plays a critical role in controlling both cell cycle progression and apoptotic cell death in response to DNA damage and oncogene activation. Following genotoxic stresses, E2F1 protein is stabilized by phosphorylation and acetylation driven to its accumulation. The aim of the present work was to examine whether the increase in E2F1 protein levels observed after DNA damage is only a reflection of an increase in E2F1 protein stability or is also the consequence of enhanced transcription of the E2F1 gene. The data presented here demonstrates that UV light and other genotoxics induce the transcription of E2F1 gene in an ATM/ATR dependent manner, which results in increasing E2F1 mRNA and protein levels. After genotoxic stress, transcription of cyclin E, an E2F1 target gene, was significantly induced. This induction was the result of two well-differentiated effects, one of them dependent on de novo protein synthesis and the other on the protein stabilization. Our results strongly support a transcriptional effect of DNA damaging agents on E2F1 expression. The results presented herein uncover a new mechanism involving E2F1 in response to genotoxic stress.
Carcagno
Abel L
AL
Laboratorio de Biología Molecular, Departamento de Química Biológica, Facultad de Ciencias Exactas y Naturales, Universidad de Buenos Aires, Ciudad Universitaria Pabellón II, 1428 Ciudad de Buenos Aires, Argentina.
Ogara
María F
MF
Sonzogni
Silvina V
SV
Marazita
Mariela C
MC
Sirkin
Pablo F
PF
Ceruti
Julieta M
JM
Cánepa
Eduardo T
ET
D064007:Ataxia Telangiectasia Mutated Proteins; D015152:Blotting, Northern; D015153:Blotting, Western; D018797:Cell Cycle Proteins / Q000378:metabolism*; D002460:Cell Line; D019927:Cyclin E / Q000378:metabolism; D004249:DNA Damage / Q000235:genetics* / Q000528:radiation effects; D050687:E2F1 Transcription Factor / Q000378:metabolism*; D006801:Humans; D009838:Oligodeoxyribonucleotides / Q000235:genetics; D010766:Phosphorylation; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism*; D015533:Transcriptional Activation / Q000235:genetics* / Q000528:radiation effects; D014466:Ultraviolet Rays
D018797:Cell Cycle Proteins; D019927:Cyclin E; D050687:E2F1 Transcription Factor; D009838:Oligodeoxyribonucleotides; C576597:ATR protein, human; D064007:Ataxia Telangiectasia Mutated Proteins; D017346:Protein Serine-Threonine Kinases