AMF1 (GPS2) Modulates p53 Transactivation

Abstract

We have reported that the papillomavirus E2 protein binds the nuclear factor AMF1 (also called G-protein pathway suppressor 2 or GPS2) and that their interaction is necessary for transcriptional activation by E2. It has also been shown that AMF1 can influence the activity of cellular transcription factors. These observations led us to test whether AMF1 regulates the functions of p53, a critical transcriptional activator that integrates stress signals and regulates cell cycle and programmed cell death. We report that AMF1 associates with p53 in vivo and in vitro and facilitates the p53 response by augmenting p53-dependent transcription. Overexpression of AMF1 in U2OS cells increases basal level p21^WAF1/CIP1 expression and causes a G₁ arrest. U2OS cells stably overexpressing AMF1 show increased apoptosis upon exposure to UV irradiation. These data demonstrate that AMF1 modulates p53 activities.

ACKNOWLEDGMENTS

We thank Karen Vousden for reviewing the manuscript and providing valuable suggestions. We are grateful to Leonard Buckbinder, Wafik El-Deiry, Steve Grossman, Moshe Owen, Kevin Ryan, and Bert Vogelstein for providing reagents. We thank members of Androphy laboratory for many useful discussions.

This work was supported by NIH grants R01 CA58376 and U01 AI38001 to E.J.A. and P30 AI42853 to C.M.