E2F6 negatively regulates ultraviolet-induced apoptosis via modulation of BRCA1.
E2F6 is believed to repress E2F-responsive genes and therefore plays an important role in cell-cycle regulation. However, the role of E2F6 in the control of apoptosis remains unknown. We show here that the expression of E2F6 was downregulated with a concurrent increase in BRCA1 mRNA and cleaved protein during ultraviolet (UV)-induced apoptosis in human embryonic kidney 293 cells. Moreover, E2F6 overexpression distinctly inhibited UV-induced apoptosis as well as UV-induced increases in BRCA1 expression and cleavage, accompanied with increases of the full-length BRCA1 and BRCA1 nuclear foci. In contrast, knockdown of E2F6 by small interfering RNA had opposite effects. Furthermore, these effects of E2F6 on BRCA1 depended upon the association of E2F6 with BRCA1 via its C-terminus in a UV-triggered manner and upon the transcriptional repression by E2F6 on the BRCA1 promoter. These findings provide the first demonstration of the important role for E2F6 in the control of apoptosis via targeting of BRCA1.
Yang
W-W
WW
Laboratory of Molecular Cardiology of Institute of Health Sciences, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences (CAS) and Shanghai Jiao Tong University School of Medicine, Shanghai, China.
Wang
Z-H
ZH
Zhu
Y
Y
Yang
H-T
HT
D017209:Apoptosis / Q000502:physiology* / Q000528:radiation effects; D019313:BRCA1 Protein / Q000096:biosynthesis*; D001665:Binding Sites / Q000235:genetics; D045744:Cell Line, Tumor; D004268:DNA-Binding Proteins / Q000032:analysis; D015536:Down-Regulation; D050701:E2F6 Transcription Factor / Q000378:metabolism*; D015972:Gene Expression Regulation, Neoplastic / Q000528:radiation effects; D019398:Genes, BRCA1 / Q000502:physiology* / Q000528:radiation effects; D006801:Humans; D007668:Kidney / Q000166:cytology; D011401:Promoter Regions, Genetic / Q000502:physiology; D012333:RNA, Messenger / Q000032:analysis; D034741:RNA, Small Interfering / Q000235:genetics; D014158:Transcription, Genetic / Q000502:physiology / Q000528:radiation effects; D015533:Transcriptional Activation / Q000502:physiology*; D014466:Ultraviolet Rays
D019313:BRCA1 Protein; D004268:DNA-Binding Proteins; D050701:E2F6 Transcription Factor; D012333:RNA, Messenger; D034741:RNA, Small Interfering