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.
Investigating the molecular basis of ARF tumor suppressor …
Feb 11, 2022 · In live cells, p14 Arf immobilizes NPM1 in nucleoli in a concentration dependent manner. Strikingly, p14 Arf expression results in the accumulation of defective 80S ribosomes in the cytoplasm, thus inhibiting protein synthesis and cell growth.
p14 ARF forms meso-scale assemblies upon phase separation with NPM1
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...
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 · NPM1 sequesters ARF inside phase-separated condensates, promoting the formation of a gel-like meso-scale network that organizes ARF into a structured assembly.
Arf mediates the nucleolar localization and inhibition of Mdm2, and inhibition of ribosome biogenesis through interactions with NPM1. We propose a new role of Arf in regulating the dynamic and composi-tional properties of the nucleolus by altering nucleolar homeostasis, via integration within the nucleolar matrix. References
Here we show that p14ARF 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...
Mutual Regulation of FOXM1, NPM and ARF Proteins - PMC
Apr 28, 2015 · It has previously been shown that FOXM1 interacts with NPM1 5 and ARF 9 and that ARF interacts with NPM1 10. Additionally, it has also been demonstrated that the knockdown of NPM leads to a down-regulation of FOXM1 (Bhat, 2011} and ARF 11 in various cell types.
NPM1 exhibits structural and dynamic heterogeneity upon phase ...
Jan 1, 2020 · Here we show that NPM1 undergoes phase separation with p14ARF in vitro, forming condensates that immobilize both proteins. We probed the structure and dynamics of NPM1 within the condensed phase using solid-state NMR spectroscopy.
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.