Russell Michael W, Soliman Mohamed A, Schriemer David, Riabowol Karl
Department of Biochemistry & Molecular Biology, Faculty of Medicine, University of Calgary, 311 HMRB, 3330 Hospital Dr. NW, Calgary, Alta., Canada T2N 4N1.
Biochem Biophys Res Commun. 2008 Sep 26;374(3):490-5. doi: 10.1016/j.bbrc.2008.07.076. Epub 2008 Jul 23.
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.
ING1蛋白通过结合组蛋白并调节染色质结构和基因表达来影响细胞凋亡、生长和DNA修复。ING1在癌症中表达下调，其在细胞质中的定位与预后不良相关。在此，我们报告ING1b通过位于ING1b PHD区域附近的几个碱性核定位序列（NLS）与核转运蛋白α2和β1相互作用。NLS基序的缺失导致ING1b无法完全定位于细胞核，并抑制了其诱导p21WAF1表达的能力。这些观察结果支持了一种普遍机制，即ING1b的活性部分通过细胞核和细胞质之间的动态亚细胞分配来调节。
