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Npm1

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Npm1

Nucleophosmin (nucleolar phosphoprotein B23, numatrin)

PDB rendering based on 2p1b.
Available structures
PDB Ortholog search: PDBe, RCSB
Identifiers
Symbols  ; B23; NPM
External IDs ChEMBL: GeneCards:
RNA expression pattern
Orthologs
Species Human Mouse
Entrez
Ensembl
UniProt
RefSeq (mRNA)
RefSeq (protein)
Location (UCSC)
PubMed search

Nucleophosmin (NPM), also known as nucleolar phosphoprotein B23 or numatrin, is a protein that in humans is encoded by the NPM1 gene.[1][2]

Function

NPM1 is associated with nucleolar ribonucleoprotein structures and bind 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. 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:[3]

  1. Histone chaperons
  2. Ribosome biogenesis and transport
  3. Genomic stability and DNA repair
  4. Endoribonuclease activity
  5. Centrosome duplication during cell cycle
  6. Regulation of ARF-p53 tumor suppressor pathway
  7. RNA helix destabilizing activity
  8. Inhibition of caspase-activated DNase
  9. Prevents apoptosis

Clinical significance

Chromosomal aberrations involving NPM1 were found in patients with non-Hodgkin lymphoma, acute promyelocytic leukemia, myelodysplastic syndrome, and acute myelogenous leukemia.[4]

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 level, 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 interact with

Nucleophosmin has multiple binding partners:[3]

  1. rRNA
  2. HIV Rev and Rex peptide
  3. p53 tumor suppressor
  4. ARF tumor suppressor
  5. MDM2 (mouse double minute 2, ubiquitin ligase)
  6. Ribosome protein S9
  7. Phosphatidylinositol 3,4,5-triphosphate (PIP3)
  8. Exportin-1 (CRM1, chromosome region maintenance)
  9. Nucleolin/C23
  10. Transcription target of myc oncogene

References

  1. ^ Liu QR, Chan PK (March 1993). "Characterization of seven processed pseudogenes of nucleophosmin/B23 in the human genome". DNA Cell Biol. 12 (2): 149–56.  
  2. ^ Morris SW, Kirstein MN, Valentine MB, Dittmer KG, Shapiro DN, Saltman DL, Look AT (March 1994). "Fusion of a kinase gene, ALK, to a nucleolar protein gene, NPM, in non-Hodgkin's lymphoma". Science 263 (5151): 1281–4.  
  3. ^ a b Lindström MS (2011). "NPM1/B23: A Multifunctional Chaperone in Ribosome Biogenesis and Chromatin Remodeling". Biochem Res Int 2011: 195209.  
  4. ^ Falini B, Nicoletti I, Bolli N, Martelli MP, Liso A, Gorello P, Mandelli F, Mecucci C, Martelli MF (April 2007). "Translocations and mutations involving the nucleophosmin (NPM1) gene in lymphomas and leukemias". Haematologica 92 (4): 519–32.  
  5. ^ Lee SB, Xuan Nguyen TL, Choi JW, Lee KH, Cho SW, Liu Z, Ye K, Bae SS, Ahn JY (October 2008). "Nuclear Akt interacts with B23/NPM and protects it from proteolytic cleavage, enhancing cell survival". Proc. Natl. Acad. Sci. U.S.A. 105 (43): 16584–9.  
  6. ^ a b Sato K, Hayami R, Wu W, Nishikawa T, Nishikawa H, Okuda Y, Ogata H, Fukuda M, Ohta T (July 2004). "Nucleophosmin/B23 is a candidate substrate for the BRCA1-BARD1 ubiquitin ligase". J. Biol. Chem. 279 (30): 30919–22.  
  7. ^ Li YP, Busch RK, Valdez BC, Busch H (April 1996). "C23 interacts with B23, a putative nucleolar-localization-signal-binding protein". Eur. J. Biochem. 237 (1): 153–8.  

Further reading

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