Nucleophosmin (NPM), also known as nucleolar phosphoprotein B23 or numatrin, is a
protein
Proteins are large biomolecules and macromolecules that comprise one or more long chains of amino acid residues. Proteins perform a vast array of functions within organisms, including catalysing metabolic reactions, DNA replication, respon ...
that in humans is encoded by the ''NPM1''
gene
In biology, the word gene (from , ; "... Wilhelm Johannsen coined the word gene to describe the Mendelian units of heredity..." meaning ''generation'' or ''birth'' or ''gender'') can have several different meanings. The Mendelian gene is a b ...
.
Function
NPM1 is associated with
nucleolar ribonucleoprotein structures and binds single-stranded and double-stranded nucleic acids, but it binds preferentially
G-quadruplex forming nucleic acids. It is involved in the biogenesis of
ribosomes and may assist small basic proteins in their transport to the
nucleolus
The nucleolus (, plural: nucleoli ) is the largest structure in the nucleus of eukaryotic cells. It is best known as the site of ribosome biogenesis, which is the synthesis of ribosomes. The nucleolus also participates in the formation of s ...
. Its regulation through
SUMOylation (by
SENP3 and
SENP5) is another facet of the protein's regulation and cellular functions.
It is located in the
nucleolus
The nucleolus (, plural: nucleoli ) is the largest structure in the nucleus of eukaryotic cells. It is best known as the site of ribosome biogenesis, which is the synthesis of ribosomes. The nucleolus also participates in the formation of s ...
, but it can be translocated to the
nucleoplasm
The nucleoplasm, also known as karyoplasm, is the type of protoplasm that makes up the cell nucleus, the most prominent organelle of the eukaryotic cell. It is enclosed by the nuclear envelope, also known as the nuclear membrane. The nucleopla ...
in case of serum starvation or treatment with anticancer drugs. The protein is
phosphorylated.
Nucleophosmin has multiple functions:
# Histone
chaperones
# Ribosome biogenesis and transport
# Genomic stability and DNA repair
# Endoribonuclease activity
#
Centrosome
In cell biology, the centrosome (Latin centrum 'center' + Greek sōma 'body') (archaically cytocentre) is an organelle that serves as the main microtubule organizing center (MTOC) of the animal cell, as well as a regulator of cell-cycle pro ...
duplication during cell cycle
# Regulation of ARF-p53 tumor suppressor pathway
# RNA helix destabilizing activity
# Inhibition of caspase-activated DNase
# Prevents apoptosis when located in nucleolus
Clinical significance
NPM1 gene is up-regulated, mutated and chromosomally translocated in many tumor types.
Chromosomal aberrations involving NPM1 were found in patients with
non-Hodgkin lymphoma,
acute promyelocytic leukemia,
myelodysplastic syndrome
A myelodysplastic syndrome (MDS) is one of a group of cancers in which immature blood cells in the bone marrow do not mature, and as a result, do not develop into healthy blood cells. Early on, no symptoms typically are seen. Later, symptoms may ...
, and
acute myelogenous leukemia.
Heterozygous mice for NPM1 are vulnerable to tumor development. In solid tumors NPM1 is frequently found overexpressed, and it is thought that NPM1 could promote tumor growth by inactivation of the tumor suppressor p53/ARF pathway; on the contrary, when expressed at low levels, NPM1 could suppress tumor growth by the inhibition of centrosome duplication.
Of high importance is NPM involvement in
acute myelogenous leukemia,
where a mutated protein lacking a folded C-terminal domain (NPM1c+) has been found in the cytoplasm in patients. This aberrant localization has been linked to the development of the disease, and is associated with improved clinical outcomes. Strategies against this subtype of acute myelogenous leukemia include the refolding of the C-terminal domain using pharmalogical chaperones and the displacement of the protein from nucleolus to nucleoplasm, which has been linked to apoptotic mechanisms. It has also been shown that in the context of clonal hematopoiesis of undetermined significance harboring a DNMT3A mutation, subsequent NPM1 mutations drive progression into overt myeloproliferative neoplasm.
Interactions
NPM1 has been shown to
interact with
*
AKT1
RAC(Rho family)-alpha serine/threonine-protein kinase is an enzyme that in humans is encoded by the ''AKT1'' gene. This enzyme belongs to the AKT subfamily of serine/threonine kinases that contain SH2 (Src homology 2-like) protein domains. I ...
,
*
BARD1,
[
* ]BRCA1
Breast cancer type 1 susceptibility protein is a protein that in humans is encoded by the ''BRCA1'' () gene. Orthologs are common in other vertebrate species, whereas invertebrate genomes may encode a more distantly related gene. ''BRCA1'' is a ...
,
References
Further reading
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{{PDB Gallery, geneid=4869
Genes on human chromosome 5