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

• Published in: Biochemical and biophysical research communications 2008-09, Vol.374 (3), p.490-495
• Main Authors: Russell, Michael W., Soliman, Mohamed A., Schriemer, David, Riabowol, Karl
• Format: Article
• Language: English
• Subjects: 60 APPLIED LIFE SCIENCES; Active Transport, Cell Nucleus; alpha Karyopherins - metabolism; Amino Acid Motifs; APOPTOSIS; beta Karyopherins - metabolism; Cell Line, Tumor; Cell Nucleus - metabolism; CHROMATIN; Cyclin-Dependent Kinase Inhibitor p21 - genetics; CYTOPLASM; DNA REPAIR; FAILURES; GENES; HISTONES; Humans; ING1; Inhibitor of Growth Protein 1; Intracellular Signaling Peptides and Proteins - genetics; Intracellular Signaling Peptides and Proteins - metabolism; Karyopherins; MONOCLINIC LATTICES; NEOPLASMS; Nuclear Localization Signals - genetics; Nuclear Localization Signals - metabolism; Nuclear Proteins - genetics; Nuclear Proteins - metabolism; Nuclear transport; PHD; Promoter Regions, Genetic; Sequence Deletion; Transcriptional Activation; Tumor Suppressor Proteins - genetics; Tumor Suppressor Proteins - metabolism
• ISSN: 0006-291X; 1090-2104
• DOI: 10.1016/j.bbrc.2008.07.076

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.