APE1 associates with 60S ribosomes and tRNAs and regulates the expression of IGF2BP1

Abstract

Apurinic/apyrimidinic endonuclease 1 (APE1), a multifunctional protein known for its DNA repair function and redox regulation, is often found overexpressed in cancers. APE1 can be found in the nucleus, cytoplasm and secreted extracellularly. APE1 subcellular distribution in the cytoplasm is frequently reported in various types of cancer but the biological significance remains unknown. In this study, APE1 in the cytoplasm of HepG2 cells was investigated using various techniques including microscopy, differential centrifugation, sucrose gradient fractionation and CL-IP. APE1 was found to associate with 60S ribosomes and tRNAs under native conditions, suggesting it may have a specific function in the translational machinery. Knockdown of APE1 in HepG2 cells led to increased protein expression of IGF2BP1 as well as enhanced HepG2 cell migration, suggesting that APE1 can act as a tumor suppressor in this cell line model of hepatocellular carcinoma. When APE1 was depleted, the translation of a reporter construct containing the 3UTR of IGF2BP1 was enhanced. This study provides evidence in support of the role of cytoplasmic APE1 in the control of IGF2BP1 protein translation and sheds light on the potential novel function of cytoplasmic APE1.