Zac1 functional interactions mediate AP-1 transcriptional activity

Abstract

A zinc-finger protein which regulates apoptosis and cell cycle arrest 1 (Zac1) is a novel seven-zinc-finger protein that can bind a specific GC-rich DNA element and has intrinsic transactivation activity; therefore, its role as a transcription factor has been proposed. Zac1 not only promotes cell cycle arrest and apoptosis but also acts as a transcriptional cofactor for nuclear receptors and p53. In this study, we examined the functional roles of mouse Zac1 (mZac1) in HeLa cells treated with 12-O-tetradecanoylphorbol-13-acetate (PMA), a potent Activator protein 1 (AP-1) activator. At first, we found that mZac1 prolonged and enhanced PMA-induced AP-1 activity in both HeLa and HeLa/p53 shRNA cells. We further identified physical and functional interactions between mZac1 and AP-1 proteins (either c-Jun, c-Fos or both). Finally, we showed that Zac1 might function as a selective coactivator of AP-1, demonstrated by AP-1-dependent transcriptional activation of collagenase, c-Fos and p21(WAF1/Cip1) promoter activities. Identification of AP-1 as a specific target for Zac1-mediated transcriptional events not only establishes a direct link between these two pivotal regulatory proteins but also raises the possibility that Zac1 contributes to certain AP-1-dependent biological effects.