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 alpha2 and beta1 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.
Russell
Michael W
MW
Department of Biochemistry & Molecular Biology, Faculty of Medicine, University of Calgary, 311 HMRB, 3330 Hospital Dr. NW, Calgary, Alta., Canada T2N 4N1.
Soliman
Mohamed A
MA
Schriemer
David
D
Riabowol
Karl
K
D021581:Active Transport, Cell Nucleus; D020816:Amino Acid Motifs; D045744:Cell Line, Tumor; D002467:Cell Nucleus / Q000378:metabolism*; D050759:Cyclin-Dependent Kinase Inhibitor p21 / Q000235:genetics*; D006801:Humans; D000076023:Inhibitor of Growth Protein 1; D047908:Intracellular Signaling Peptides and Proteins / Q000235:genetics / Q000378:metabolism*; D019913:Nuclear Localization Signals / Q000235:genetics / Q000378:metabolism; D009687:Nuclear Proteins / Q000235:genetics / Q000378:metabolism*; D011401:Promoter Regions, Genetic; D017384:Sequence Deletion; D015533:Transcriptional Activation; D025521:Tumor Suppressor Proteins / Q000235:genetics / Q000378:metabolism*; D028901:alpha Karyopherins / Q000378:metabolism*; D028961:beta Karyopherins / Q000378:metabolism*
C493956:CDKN1A protein, human; D050759:Cyclin-Dependent Kinase Inhibitor p21; C501503:ING1 protein, human; D000076023:Inhibitor of Growth Protein 1; D047908:Intracellular Signaling Peptides and Proteins; C423142:KPNA1 protein, human; C424166:KPNB1 protein, human; D019913:Nuclear Localization Signals; D009687:Nuclear Proteins; D025521:Tumor Suppressor Proteins; D028901:alpha Karyopherins; D028961:beta Karyopherins