NPM1
Encyclopedia
Nucleophosmin also known as nucleolar phosphoprotein B23 or numatrin, is a protein
that in humans is encoded by the NPM1 gene
.
ribonucleoprotein
structures and bind single-stranded nucleic acids. It is involved in the biogenesis of ribosome
s and may assist small basic proteins in their transport to the nucleolus
. Its regulation through SUMOylation (by SENP3
and SENP5) is another facet of the proteins's regulation and cellular functions.
It is located in the nucleolus
, but it can be translocated to the nucleoplasm
in case of serum starvation or treatment with anticancer drugs. The protein is phosphorylated.
Nucleophosmin has multiple functions:
, acute promyelocytic leukemia
, myelodysplastic syndrome
, and acute myelogenous leukemia.
It has been found in the cytoplasm in patients with primary acute myelogenous leukemia.
NPM1 roles in tumorigenesis: NPM1 gene is up-regulated, mutated and chromosomally translocated in many tumor types. NPM1 is transferred from nucleolus to nucleoplasm and cytoplasm by anticancer drugs. When expressed at high level, NPM1 could promote tumor growth by inactivation of tumor suppressor p53/ARF pathway; when expressed at low lever, NPM1 could suppress tumor growth by inhibition of centrosome duplication. NPM1 is haploinsufficient in hemizygous mice that are vulnerable to tumor development. NPM1c+ (cytoplasm form) translocation into cytoplasm could serve as AML remission signal. NPM1 forms pentamer that could serve as a potential anticancer drug target.
with
Nucleophosmin has multiple binding partners:
Protein
Proteins are biochemical compounds consisting of one or more polypeptides typically folded into a globular or fibrous form, facilitating a biological function. A polypeptide is a single linear polymer chain of amino acids bonded together by peptide bonds between the carboxyl and amino groups of...
that in humans is encoded by the NPM1 gene
Gene
A gene is a molecular unit of heredity of a living organism. It is a name given to some stretches of DNA and RNA that code for a type of protein or for an RNA chain that has a function in the organism. Living beings depend on genes, as they specify all proteins and functional RNA chains...
.
Function
NPM1 is associated with nucleolarNucleolus
The nucleolus is a non-membrane bound structure composed of proteins and nucleic acids found within the nucleus. Ribosomal RNA is transcribed and assembled within the nucleolus...
ribonucleoprotein
Ribonucleoprotein
Ribonucleoprotein is a nucleoprotein that contains RNA, i.e. it is an association that combines ribonucleic acid and protein together. A few known examples include the ribosome, the enzyme telomerase, vault ribonucleoproteins, and small nuclear RNPs , which are implicated in pre-mRNA splicing and...
structures and bind single-stranded nucleic acids. It is involved in the biogenesis of ribosome
Ribosome
A ribosome is a component of cells that assembles the twenty specific amino acid molecules to form the particular protein molecule determined by the nucleotide sequence of an RNA molecule....
s and may assist small basic proteins in their transport to the nucleolus
Nucleolus
The nucleolus is a non-membrane bound structure composed of proteins and nucleic acids found within the nucleus. Ribosomal RNA is transcribed and assembled within the nucleolus...
. Its regulation through SUMOylation (by SENP3
SENP3
SUMO1/sentrin/SMT3 specific peptidase 3, also known as SENP3, is a protein which in humans is encoded by the SENP3 gene.SENP3 together with SENP5, belongs to the Ulp1 branch in yeast and localize to nucleolus through B23/NPM1. SENP3 is associated and regulated by B23/nucleophosmin/NPM1 and involved...
and SENP5) is another facet of the proteins's regulation and cellular functions.
It is located in the nucleolus
Nucleolus
The nucleolus is a non-membrane bound structure composed of proteins and nucleic acids found within the nucleus. Ribosomal RNA is transcribed and assembled within the nucleolus...
, but it can be translocated to the nucleoplasm
Nucleoplasm
Similar to the cytoplasm of a cell, the nucleus contains nucleoplasm or karyoplasm. The nucleoplasm is one of the types of protoplasm, and it is enveloped by the nuclear membrane or nuclear envelope. The nucleoplasm is a highly viscous liquid that surrounds the chromosomes and nucleoli...
in case of serum starvation or treatment with anticancer drugs. The protein is phosphorylated.
Nucleophosmin has multiple functions:
- Histone chaperons
- Ribosome biogenesis and transport
- Genomic stability and DNA repair
- Endoribonuclease activity
- Centrosome duplication during cell cycle
- Regulation of ARF-p53 tumor suppressor pathway
- RNA helix destabilizing activity
- Inhibition of caspase-activated DNase
- Prevents apoptosis
Clinical significance
Chromosomal aberrations involving NPM1 were found in patients with non-Hodgkin lymphomaNon-Hodgkin lymphoma
The non-Hodgkin lymphomas are a diverse group of blood cancers that include any kind of lymphoma except Hodgkin's lymphomas. Types of NHL vary significantly in their severity, from indolent to very aggressive....
, acute promyelocytic leukemia
Acute promyelocytic leukemia
Acute promyelocytic leukemia is a subtype of acute myelogenous leukemia , a cancer of the blood and bone marrow. It is also known as acute progranulocytic leukemia; APL; AML with t, PML-RARA and variants; FAB subtype M3 and M3 variant.In APL, there is an abnormal accumulation of immature...
, myelodysplastic syndrome
Myelodysplastic syndrome
The myelodysplastic syndromes are a diverse collection of hematological medical conditions that involve ineffective production of the myeloid class of blood cells....
, and acute myelogenous leukemia.
It has been found in the cytoplasm in patients with primary acute myelogenous leukemia.
NPM1 roles in tumorigenesis: NPM1 gene is up-regulated, mutated and chromosomally translocated in many tumor types. NPM1 is transferred from nucleolus to nucleoplasm and cytoplasm by anticancer drugs. When expressed at high level, NPM1 could promote tumor growth by inactivation of tumor suppressor p53/ARF pathway; when expressed at low lever, NPM1 could suppress tumor growth by inhibition of centrosome duplication. NPM1 is haploinsufficient in hemizygous mice that are vulnerable to tumor development. NPM1c+ (cytoplasm form) translocation into cytoplasm could serve as AML remission signal. NPM1 forms pentamer that could serve as a potential anticancer drug target.
Interactions
NPM1 has been shown to interactProtein-protein interaction
Protein–protein interactions occur when two or more proteins bind together, often to carry out their biological function. Many of the most important molecular processes in the cell such as DNA replication are carried out by large molecular machines that are built from a large number of protein...
with
- AKT1AKT1RAC-alpha serine/threonine-protein kinase is an enzyme that in humans is encoded by the AKT1 gene. Multiple alternatively spliced transcript variants have been found for this gene.- Function :...
, - BARD1BARD1BRCA1-associated RING domain protein 1 is a protein that in humans is encoded by the BARD1 gene.-Interactions:BARD1 has been shown to interact with BRE, UBE2D1, CSTF2, BRCC3, RAD51, BCL3, TACC1, Ewing sarcoma breakpoint region 1, FANCD2, H2AFX, CSTF1, NPM1, BRCA2, BRCA1, P53 and Aurora B...
, - BRCA1BRCA1BRCA1 is a human caretaker gene that produces a protein called breast cancer type 1 susceptibility protein, responsible for repairing DNA. The first evidence for the existence of the gene was provided by the King laboratory at UC Berkeley in 1990...
, and - nucleolinNucleolinNucleolin is a protein that in humans is encoded by the NCL gene.- Gene :The human NCL gene is located on chromosome 2 and consists of 14 exons with 13 introns and spans approximately 11kb...
.
Nucleophosmin has multiple binding partners:
- rRNA
- HIV Rev and Rex peptide
- p53 tumor suppressor
- ARF tumor suppressor
- MDM2 (mouse double minute 2, ubiquitin ligase)
- Ribosome protein S9
- Phosphatidylinositol 3,4,5-triphosphate (PIP3)
- Exportin-1 (CRM1, chromosome region maintenance)
- Nucleolin/C23
- Transcription target of myc oncogene