The tumor suppressor p33ING1b upregulates p16INK4a expression and induces cellular senescence

ING1 protein is a tumor suppressor which plays significant roles in multiple cellular activities. p47ING1a and p33ING1b 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 p16INK4a. We observe that p33ING1b protein is the major ING1 isoform expressed in 2BS human diploid fibroblasts. Overexpression of p33ING1b induces cellular senescence and upregulates p16INK4a expression in 2BS fibroblasts. p33ING1b upregulates p16INK4a transcription. p33ING1b and p300 bind to the p16INK4a promoter. p300/CBP-specific inhibitor curcumin can reverse the induction of p16INK4a by p33ING1b. These results help to better understand the function of ING1.

► p33ING1b is the major splice isoform of ING1 in human 2BS fibroblasts.
► p33ING1b induces cellular senescence and p16INK4a expression.
► p16INK4a expression is upregulated by p33ING1b at the transcriptional level.
► p300/CBP HAT plays a part in p16INK4a induction by p33ING1b.