This study provides the following insight; the elucidation of a novel mechanism by which NPM1 recruits Mdm2 to promote the ubiquitin-mediated degradation of p53, which results in the inhibition of the p53-related signaling pathway both in vitro and in vivo.

2024年11月11日 · Oncogenic stress induces p14 ARF to inhibit MDM2, stabilize p53 and arrest the cell cycle. Under non-stress conditions, NPM1 stabilizes p14 ARF in nucleoli, preventing its degradation and...

NPM1 promotes nasopharyngeal carcinoma metastasis and stemness by recruiting Mdm2 to induce the ubiquitination-mediated degradation of p53. Nasopharyngeal carcinoma (NPC) is clinically challenging due to the development of distant metastasis following initial therapy.

2016年12月22日 · Here we demonstrate a mutually regulatory relationship between STAT5 and NPM1. Induction of STAT5 phosphorylation at Y694 (P-STAT5) diminished NPM1 expression, whereas inhibition of STAT5...

2024年12月17日 · The mammalian sirtuin SIRT7 promotes deacetylation of NPM1 that is necessary for the stress-dependent relocation of NPM1 into the nucleoplasm and MDM2 binding, thereby...

2023年1月1日 · NPM1 and p14ARF each bind MDM2, stabilizing p53. NPM1 also activates caspase-2 via the PIDDosome. These pathways result in cell cycle arrest, senescence, or apoptosis.

NPM1 stabilizes both TP53 and MDM2, the TP53 negative regulator, hence modulating cellular growth suppression through p53-dependent and independent mechanisms. Loss of NPM1 could affect levels of TP53, leading to oncogenic transformation.

2023年5月15日 · Mechanistic analyses revealed that the E3 ubiquitin ligase Mdm2 was recruited by NPM1 to induce the ubiquitination-mediated proteasomal degradation of p53. Ultimately, knockdown of NPM1 suppressed the stemness and EMT signals.

2014年3月10日 · Our manuscript describes that the N-terminal domain of NPM1 (Npm-N) exhibits phosphorylation-dependent structural polymorphism along a broad conformational landscape between two extreme states: a stable, folded pentamer and a globally disordered monomer.

2019年1月10日 · The NPM1-MDM2 interaction is particularly enhanced upon NPM1 nuclear relocalization following nucleolar stress and this pathway is currently being investigated for the development of novel therapies in NPM1-mutated AML through nucleolar stress induction .