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.