Nucleoplasmic mobilization of nucleostemin stabilizes MDM2 and promotes G2-M progression and cell survival.

ABSTRACT: Nucleolar disassembly occurs during mitosis and nucleolar stress, releasing several MDM2-interactive proteins residing in the nucleolus that share the common activity of p53 stabilization. Here, we demonstrate that mobilization of nucleostemin, a nucleolar protein enriched in cancer and stem cells, has the opposite role of stabilizing MDM2 and suppressing p53 functions. Our results show that nucleostemin increases the protein stability and nucleoplasmic retention of MDM2, and competes with L23 for MDM2 binding. These activities were significantly elevated when nucleostemin is released into the nucleoplasm by mutations that abolish its nucleolar localization or by chemotherapeutic agents that disassemble the nucleoli. Nucleostemin depletion decreases MDM2 protein, increases transcription ac

SUBMITTER: Meng L 

PROVIDER: S-EPMC5048913 | biostudies-literature | 2008 Dec

REPOSITORIES: biostudies-literature