ING1 protein targeting to the nucleus by karyopherins is necessary for activation of p21

ING1 proteins affect apoptosis, growth, and DNA repair by binding histones and regulating chromatin structure and gene expression. ING1 is downregulated in cancers and cytoplasmic localization is associated with poor prognosis. Here, we report that ING1b interacts with karyopherins α2 and β1 through several basic nuclear localization sequences (NLS) located adjacent to the ING1b PHD region. Deletion of NLS motifs resulted in failure of ING1b to completely localize to the nucleus and inhibited its ability to induce p21WAF1 expression. These observations support a general mechanism by which ING1b activity is regulated, in part, through dynamic subcellular partitioning between the nucleus and cytoplasm.