Nucleophosmin 1 Mutations in Acute Myeloid Leukemia - PMC
The tumor suppressor Arf residing in the nucleolus is stabilized by NPM1. Arf is delocalized to the cytoplasm by NPM1c, which in turn exerts a dominant negative effect on wild-type NPM1, and it limits the inhibitory effect of NPM1 on this protein’s turnover, thus decreasing the half-life of Arf .
Functions of the native NPM1 protein and its leukemic mutant
Dec 17, 2024 · In this review, we focus on the functions of the native NPM1 protein and how its mutant contributes to promote and maintain acute myeloid leukemia (AML).
p14 ARF forms meso-scale assemblies upon phase separation …
Nov 11, 2024 · Here we show that p14 ARF assembles into a gel-like meso-scale network upon phase separation with NPM1. This assembly is mediated by intermolecular contacts formed by hydrophobic residues in an...
Biological and clinical consequences of NPM1 mutations in AML
Jan 23, 2017 · NPM1c and Arf tumor suppressor. As mentioned above, Arf tumor suppressor activity is dependent upon interaction with NPM1 for stabilization and localization.
On the relationship status for Arf and NPM1–it’s complicated
Through multivalent interactions with NPM1 – a regulator of ribosome biogenesis, and Mdm2 – a regulator of cellular fate, Arf integrates within the nucleolar matrix, altering its structure, dynamics and function and therefore modulates the cell cycle.
Mutant NPM1 Directly Regulates Oncogenic Transcription in
Mar 1, 2023 · We demonstrate that NPM1c directly regulates oncogenic gene expression in collaboration with the MLL1 complex and define the mechanism by which MLL1-Menin small-molecule inhibitors produce clinical responses in patients with NPM1-mutated AML.
Mutant NPM1 Directly Regulates Oncogenic Transcription in Acute …
Mar 1, 2023 · We demonstrate that NPM1c directly regulates oncogenic gene expression in collaboration with the MLL1 complex and define the mechanism by which MLL1–Menin small-molecule inhibitors produce clinical responses in patients with NPM1 -mutated AML.
Targeted therapy in NPM1-mutated AML: Knowns and unknowns
Mutated NPM1 result in the cytoplasmic localization of NPM1 (NPM1c). NPM1c interacts with other proteins to block myeloid differentiation, promote cell proliferation and impair DNA damage repair. NPM1 is a good prognostic marker, but some …
Induction and Therapeutic Targeting of Human NPM1c
Mar 3, 2019 · Mutant NPM1, also referred to as NPM1c because of its predominantly cytoplasmic localization, has been shown to destabilize the p19 (Arf) tumor suppressor 8 and prevent the degradation of Myc 9,10.
Nucleophosmin: from structure and function to disease …
Aug 24, 2016 · Nucleophosmin (NPM1), also known as B23, No38 or Numatrin, is an abundant nucleolar protein found in the nuclei of proliferating cells. NPM1 has been documented as participating in ribosome biogenesis, mRNA processing, chromatin remodeling, and embryogenesis (Fig. 1).