The tumor suppressor p33ING1b upregulates p16INK4a expression and induces cellular senescence

Abstract

ING1 protein is a tumor suppressor which plays significant roles in multiple cellular activities. p47(ING1a) and p33(ING1b) are major splice isoforms of ING1 and their roles in senescence need further investigations. Here we studied the functions of ING1 isoforms in cellular senescence and gene regulation, with focus on p16(INK4a). We observe that p33(ING1b) protein is the major ING1 isoform expressed in 2BS human diploid fibroblasts. Overexpression of p33(ING1b) induces cellular senescence and upregulates p16(INK4a) expression in 2BS fibroblasts. p33(ING1b) upregulates p16(INK4a) transcription. p33(ING1b) and p300 bind to the p16(INK4a) promoter. p300/CBP-specific inhibitor curcumin can reverse the induction of p16(INK4a) by p33(ING1b). These results help to better understand the function of ING1.