NPM1 contributes to the p53 stress response by modulating the activity and stability of p53 and the Arf tumor suppressor protein. NPM1 interacts directly with p53, regulating an increase in the stability and transcriptional activation of p53 after different types of stress [ 35 ].

Dec 22, 2016 · This study reveals a new STAT5 signaling pathway regulating p53 expression via NPM1 and uncovers new therapeutic targets for anticancer treatment in tumors driven by STAT5 signaling.

A mutation of the NPM1 gene resulting in the altered C-terminus of NPM and aberrant localization of mutated NPM to the cytoplasm appears in approximately 50% AML with normal karyotype [10,29,30]. Leukemogenic potential of the mutation has not been elucidated yet.

Nov 25, 2016 · Compared with wild-type NPM1 that can disrupt the p53–HDM2 interaction, the C275S mutant greatly compromises the activation of p53, highlighting that nucleoplasmic translocation of NPM1 is a...

NPM1 directly binds to MDM2, hindering its inhibitory role on p53. Notably, this NPM1 mechanism indirectly affects p53 activity as indicated by studies on NPM1-negative mice and embryo cell lines that still express p53.

Dec 17, 2024 · In unstressed cells, p14ARF and NPM1 form a dimer in the nucleoli, allowing MDM2 to target p53 causing its nuclear export and proteasomal degradation, which allows to maintain the p53 levels low.

Aug 24, 2016 · These observations provide evidence that NPM1 regulates cell fate in a p53-dependent manner by directing p14 ARF to nucleoli and preventing inhibition of MDM2 (Fig. 4) [27, 30, 31]. Other studies have also linked NPM1 with the tumor suppressor activity of p53.

Aug 1, 2024 · Nucleophosmin 1 (NPM1) is a multifunctional protein that plays a pivotal role in various cellular processes, including ribosome biogenesis, centrosome duplication, and regulation of the p14ARF-p53 tumor-suppressor pathway [40], [41].

Aug 7, 2018 · We show here that the expression of NPM1 is regulated by transcription factor c-fos, a protein that is strongly activated by growth factor signals. In addition, mutant p53 (R175H) overexpression also enhances NPM1 expression possibly through c-myc and c-fos.

May 28, 2021 · NPM1+/TP53+ AML had more mutations in recurrently mutated genes (4.5 vs 2.1; P < 0.0001) than TP53+/NPM1- AML. Conclusions: TP53+/NPM1+ AML harbors molecular signatures which clearly distinguish it from ordinary TP53-mutated AML, and is more reflective of de novo and NPM1+ AML.