Nucleophosmin in Its Interaction with Ligands
Ilaria Cela1,2, Adele Di Matteo3, Luca Federici1,2
1Center for Advanced Studies and Technology (CAST), University of Chieti "G. d'Annunzio", Via Polacchi, 66100 Chieti, Italy.
International Journal of Molecular Sciences
|July 16, 2020
Summary
Nucleophosmin (NPM1) is a key nucleolar protein involved in numerous cellular processes. NPM1 inhibitors show therapeutic potential for cancers and other diseases by disrupting its interactions.
Area of Science:
- Molecular Biology
- Cell Biology
- Biochemistry
Background:
- Nucleophosmin (NPM1) is a crucial nucleolar protein with diverse cellular functions, including acting as a chaperone and regulating cell cycle.
- NPM1 is implicated in various cancers due to alterations like overexpression and mutations.
- Recent findings link NPM1 germline mutations to dyskeratosis congenita.
Purpose of the Study:
- This review focuses on the interactions of NPM1 and the development of NPM1 inhibitors.
- To explore the structural basis of NPM1's interactions with nucleic acids and proteins.
- To discuss the emerging therapeutic potential of NPM1 inhibitors.
Main Methods:
- Literature review of studies on NPM1 interactions and inhibition.
- Analysis of structural data for NPM1 binding partners.
- Compilation of reported natural and synthetic NPM1 ligands.
Main Results:
- NPM1 interacts with a growing list of nucleic acids and proteins, crucial for its functions.
- The structural basis for NPM1 recognition of its binding partners is increasingly understood.
- Various ligands capable of interfering with NPM1 interactions have been identified.
Conclusions:
- NPM1 is a central hub protein with significant roles in cellular organization and stress response.
- Understanding NPM1 interactions is key to developing targeted therapies.
- NPM1 inhibitors represent a promising new therapeutic strategy for cancers and other pathologies.
Keywords:
AMLB23acute myeloid leukemiacancernucleophosminprotein–nucleic acids interactionsprotein–protein interactionsMore Related Videos
09:38Identification of Nucleolar Factors During HIV-1 Replication Through Rev Immunoprecipitation and Mass Spectrometry
Published on: June 26, 2019
8.4K
10:28Measuring Interactions of Globular and Filamentous Proteins by Nuclear Magnetic Resonance Spectroscopy NMR and Microscale Thermophoresis MST
Published on: November 2, 2018
12.5K
Related Concept Videos
01:45Regulation of Nuclear Protein Sorting
3.1K
Nuclear protein sorting regulates nucleus composition and gene expression, crucial for determining the fate of a eukaryotic cell. Hence, the entry and exit of molecules across the nuclear envelope is a tightly controlled process. Nuclear protein sorting can be inhibited by one of the following ways: 1) masking cargo signal sequences, 2) modifying the nuclear receptor's affinity for cargo, 3) controlling the nuclear pore size, 4) retaining the cargo during its transit to the cytosol or the...
3.1K
01:34Nuclear Protein Sorting
6.0K
Nuclear protein sorting is the selective trafficking of histones, polymerases, gene regulatory proteins into the nucleus and exporting RNAs and ribosomes to the cytosol. It is a tightly controlled process that regulates gene expression within a cell.
Proteins targeted to the nucleus carry nuclear localization signals or NLS recognized by import receptors in the cytosol. Similarly, proteins with nuclear export signals are recognized by export receptors. Import and export receptors are...
Proteins targeted to the nucleus carry nuclear localization signals or NLS recognized by import receptors in the cytosol. Similarly, proteins with nuclear export signals are recognized by export receptors. Import and export receptors are...
6.0K
02:04Covalently Linked Protein Regulators
8.4K
Proteins can undergo many types of post-translational modifications, often in response to changes in their environment. These modifications play an important role in the function and stability of these proteins. Covalently linked molecules include functional groups, such as methyl, acetyl, and phosphate groups, and also small proteins, such as ubiquitin. There are around 200 different types of covalent regulators that have been identified.
These groups modify specific amino acids in a protein....
These groups modify specific amino acids in a protein....
8.4K
02:55The Nucleolus
10.0K
The nucleolus is the most prominent substructure of the nucleus. When it was first discovered, it was considered to be an isolated organelle that forms fibrils and granules. In 1931, the relationship between the nucleolus and chromosomes was first described by Heitz. He observed that the appearance and size of nucleolus varies depending on the stage of the cell cycle. He also noticed constricted regions on different chromosomes clustered together at definite cell cycle stages. These regions,...
10.0K
01:46Nuclear Localization Signals and Import
7.4K
Proteins targeted to the nucleus carry short stretches of amino acid sequences called the nuclear localization signal or NLS. Classical nuclear localization signals are of two types: monopartite and bipartite NLS. Monopartite classical NLS (cNLS) consists of a single cluster of 4-8 amino acids. Bipartite cNLS consists of two clusters of 2-3 amino acids and a 9-12 residue long proline-rich linker bridging the two clusters. Signal clusters are rich in positively charged amino acids such as...
7.4K
00:49Ligand Binding and Linkage
5.3K
Allosteric proteins have more than one ligand binding site; the binding of a ligand to any of these sites influences the binding of ligands to the other sites. When a protein is allosteric, its binding sites are called coupled or linked. In the case of enzymes, the site that binds to the substrate is known as the active site and the other site is known as the regulatory site. When a ligand binds to the regulatory site, this leads to conformational changes in the protein that can influence...
5.3K