NPM1

Official Full Name

nucleophosmin 1

Organism

Homo sapiens

Gene ID

4869

Background

The protein encoded by this gene is involved in several cellular processes, including centrosome duplication, protein chaperoning, and cell proliferation. The encoded phosphoprotein shuttles between the nucleolus, nucleus, and cytoplasm, chaperoning ribosomal proteins and core histones from the nucleus to the cytoplasm. This protein is also known to sequester the tumor suppressor ARF in the nucleolus, protecting it from degradation until it is needed. Mutations in this gene are associated with acute myeloid leukemia. Dozens of pseudogenes of this gene have been identified. [provided by RefSeq, Aug 2017]

Synonyms

B23; NPM

Cat.No.	Product Name	Price
CSC-DC010558	Panoply™ Human NPM1 Knockdown Stable Cell Line	Inquiry
CSC-SC010558	Panoply™ Human NPM1 Over-expressing Stable Cell Line	Inquiry

Cat.No.	Product Name	Price
AD10948Z	Human NPM1 adenoviral particles	Inquiry

Cat.No.	Product Name	Price
SHH354316	shRNA set against Mouse NPM1 (NM_008722.3)	Inquiry
SHH354312	shRNA set against Human NPM1 (NM_199185.3)	Inquiry
SHH354320	shRNA set against Rat NPM1 (NM_012992.4)	Inquiry
SHW005762	shRNA set against Chicken NPM1 (NM_205267)	Inquiry

Cat.No.	Product Name	Price
CDCB160269	Human NPM1 ORF clone (NM_002520)	Inquiry
CDCB167237	Chicken NPM1 ORF Clone (NM_205267)	Inquiry
MiUTR3H-01576	NPM1 miRNA 3'UTR clone	Inquiry
MiUTR3H-01577	NPM1 miRNA 3'UTR clone	Inquiry
MiUTR3H-01578	NPM1 miRNA 3'UTR clone	Inquiry
CDCB182282	Rabbit NPM1 ORF clone (XM_008255384.1)	Inquiry
CDCB195158	Rabbit NPM1 ORF clone (NM_001171319.1)	Inquiry
CDCR377836	Rat Npm1 ORF Clone(NM_012992.4)	Inquiry
CDCS406915	Human NPM1 ORF Clone (BC002398)	Inquiry
CDCS406916	Human NPM1 ORF Clone (BC021983)	Inquiry
CDCS406917	Human NPM1 ORF Clone (BC016768)	Inquiry
CDCS406918	Human NPM1 ORF Clone (BC009623)	Inquiry
CDCS406919	Human NPM1 ORF Clone (BC003670)	Inquiry
CDCS406920	Human NPM1 ORF Clone (BC012566)	Inquiry

Detailed Information

NPM1 (Nucleophosmin, also known as B23, Numatrin or N038) is a nucleoprotein that is mainly located in the nucleoli and can shuttle between the nucleoli and the cytoplasm. It is widely expressed in various types of cells. The gene is located on chromosome 5q35, with a total of 12 exons, of which the 12th exon is longer (358 bp). Its encoded nucleoplasmic shuttle protein (riboprotein) has a variety of important functions, such as blocking the nucleolar protein. NPM1 aggregates, regulates the assembly of ribosomal proteins and the transport of these proteins between the nucleus and the plasm, and initiates centrosome folding. In addition, it also affects ARF, P53 and other tumor suppressor pathways.

Npm1 Figure 1. NPM1 functions as an rRNA 2´-O-Me regulator. (Zhou, F., et al. 2019)

NPM1 Features

NPM1 plays an important role in regulating ribosome biosynthesis and centrosome replication. When the NPM1 gene is mutated, these functions are severely inhibited, which affects cell growth. NPM1 can regulate the activity and stability of key tumor inhibitors ARF, p53 and MDM2, thereby changing the progress of the cell cycle. ARF can disrupt the precursor processing of rRNA and inhibit ribosome biosynthesis, inhibit cell growth, and change the cell cycle. The activation of p53 can arrest the damaged cells in G0/G1 phase or enter apoptosis. NPM1 overexpression can cause significant up-regulation of p53, MDM2, and p21 protein expression levels in fibroblasts. The mechanism may be that NPM1 directly interacts with MDM2 to inhibit the degradation of p53, and regulates the assembly of p53 modification complexes to regulate the activation and stability of p53, thus playing a dual role in regulating p53 activity.

NPM1 and Acute Myeloid Leukemia (AML)

In recent years, with the in-depth study of the pathogenesis of AML, it has been found that the occurrence and development of AML are closely related to FLT3-ITD, DNMT3A and NPM1 and other proteins, and play an important role in the treatment and prognosis of AML. NPM1 is one of the proteins most associated with AML that is currently found. The NPM1 mutation is mainly found in acute myeloid leukemia (AML), and its mutation rate accounts for about 33% of AML. The NPM1 gene is also involved in the development of many hematological malignancies. Various chromosomal translocations are the main features of NPM1. A recent study in CD30-positive lymphoproliferative disease (LPD) found that NPM1-TYK2 t (5; 19) (appeared in q35; p13) translocation. In addition, there is a translocation of NPM1-HAUS1 t (5; 18) (q35; q31) in AML.

When NPM1 functions as an oncogene, it can cause an increase in ribosome biosynthesis, thereby inhibiting apoptosis. When the expression of NPM1 decreases due to insufficient haploids or changes in subcellular localization, NPM1 becomes a cancer suppressor. It can also reduce the occurrence of leukemia through ARF tumor suppressor pathway and increase genomic instability mechanism. The most common NK-AML is the NPM1 mutation located in exon 12, which is mainly inserted into the four nucleotides of TCTG, resulting in frameshift mutations that cause corresponding changes in biological functions and affect the prognosis. There are three types of mutations A, B, and D. Among them, the overall survival rate of patients with type A mutation is the lowest, and type D is the highest. NPM1 can modulate the activity and stability of key tumor suppressors RF, p53 and MDM2, thereby changing the cell cycle and promoting the occurrence of AML through the regulation of cell mitosis.

References:

Zhou, F., & Müller-Tidow, C. (2019). NPM1 functions in epitranscriptomics. Nature Genetics, 51(10), 1436-1437.
Brunetti, L., Gundry, M. C., Sorcini, D., Guzman, A. G., Huang, Y. H., Ramabadran, R., ... & Buckley, D. L. (2018). Mutant NPM1 maintains the leukemic state through HOX expression. Cancer Cell, 34(3), 499-512.

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