Activating transcription factor 3 mediates apoptotic functions through a p53-independent pathway in human papillomavirus 18 infectedHeLa cells.

Abstract

Activating transcription factor 3 (ATF3) is the first p53 stability regulator that interferes with the ubiquitination of p53. However, the E6 oncoprotein of high-risk human papillomaviruses (HPVs) binds to and induces proteasome-dependent degradation of the host p53 protein. Herein, we investigate the effects of ATF3overexpression on cell cycle progression andapoptosis in HPV-18-infected HeLa cells, and further examinewhether ATF3 could alter the apoptosis level of HeLa cells through the inhibition of E6-mediated p53 degradation. Cytological function of HeLa cells prior and subsequent to the overexpression of ATF3 was assessed using cell cycle and annexin V/PI flow cytometry analysis. Western blotting assays revealed no significant effect of ATF3 on the levels of p53 and E6 in HeLa cells. However, annexin V stainingdemonstrated increases in apoptosis. ATF3 acts as a tumor suppressor factor in HPV18-related cervical cancer which mediates apoptotic functions through a p53-independent pathway.