We show that expression levels of ERIC were elevated upon activation of exogenous E2F1, E2F3 or endogenous E2Fs. Moreover, knockdown of either E2F1 or E2F3 reduced ERIC levels and endogenous E2F1 binds ERIC's promoter. Expression of ERIC was cell cycle regulated and peaked in G1 in an E2F1-dependent manner. Inhibition of ERIC expression increased E2F1-mediated apoptosis, suggesting that E2F1 and ERIC constitute a negative feedback loop that modulates E2F1 activity. Furthermore, ERIC levels were increased following DNA damage by the chemotherapeutic drug Etoposide, and inhibition of ERIC expression enhanced Etoposide -induced apoptosis.