ARF Impedes NPM/B23 Shuttling in an Mdm2-Sensitive Tumor Suppressor Pathway

• DOI: 10.1128/mcb.24.21.9327-9338.2004
• Publication Date: 2004-10-14T00:38:32Z
• Authors: Suzanne N. Brady; Yue Yu; Leonard B. Maggi; Jason D. Weber
• Keywords: Nucleophosmin; p14arf

The ARF tumor suppressor is widely regarded as an upstream activator of p53-dependent growth arrest and apoptosis.However, recent findings indicate that can also regulate the cell cycle in absence p53.In search p53-independent targets, we isolated nucleophosmin (NPM/B23), a protein show required for proliferation, novel binding protein.In response to hyperproliferative signals, upregulated, resulting nucleolar retention NPM concomitant arrest.The Mdm2 oncogene outcompetes NPM/B23 binding, introduction reverses ARF's properties: vitro, released from ARF-containing complexes, vivo S phase progression ensues.ARF induction by oncogenes or replicative senescence does not alter levels but rather prevents its nucleocytoplasmic shuttling without inhibiting rRNA processing.By actively sequestering nucleolus, utilizes additional mechanism suppression, one readily antagonized Mdm2.