View source for NPM1

{{Infobox_gene}}
'''Nucleophosmin''' (NPM), also known as '''nucleolar phosphoprotein B23''' or  '''numatrin''', is a [[protein]] that in humans is encoded by the ''NPM1'' [[gene]].<ref name="pmid8471164">{{cite journal | vauthors = Liu QR, Chan PK | title = Characterization of seven processed pseudogenes of nucleophosmin/B23 in the human genome | journal = DNA Cell Biol. | volume = 12 | issue = 2 | pages = 149–56 |date=March 1993 | pmid = 8471164 | doi = 10.1089/dna.1993.12.149| url =  }}</ref><ref name="pmid8122112">{{cite journal | vauthors = Morris SW, Kirstein MN, Valentine MB, Dittmer KG, Shapiro DN, Saltman DL, Look AT | title = Fusion of a kinase gene, ALK, to a nucleolar protein gene, NPM, in non-Hodgkin's lymphoma | journal = Science | volume = 263 | issue = 5151 | pages = 1281–4 |date=March 1994 | pmid = 8122112 | doi = 10.1126/science.8122112| url = http://www.sciencemag.org/cgi/pmidlookup?view=long&pmid=8122112 }}</ref>

== Function ==

NPM1 is associated with [[Nucleolus|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 [[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:<ref name="pmid21152184">{{cite journal | author = Lindström MS | title = NPM1/B23: A Multifunctional Chaperone in Ribosome Biogenesis and Chromatin Remodeling | journal = Biochem Res Int | volume = 2011 | issue = | pages = 195209 | year = 2011 | pmid = 21152184 | pmc = 2989734 | doi = 10.1155/2011/195209 | url =  }}</ref>
# Histone [[Chaperone (protein)|chaperones]]
# 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 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]], and [[acute myelogenous leukemia]].<ref name="pmid17488663">{{cite journal | vauthors = Falini B, Nicoletti I, Bolli N, Martelli MP, Liso A, Gorello P, Mandelli F, Mecucci C, Martelli MF | title = Translocations and mutations involving the nucleophosmin (NPM1) gene in lymphomas and leukemias | journal = Haematologica | volume = 92 | issue = 4 | pages = 519–32 |date=April 2007 | pmid = 17488663 | doi = 10.3324/haematol.11007| url = http://www.haematologica.org/cgi/pmidlookup?view=long&pmid=17488663 }}</ref> 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]],<ref name="MeaniAlcalay2014">{{cite journal|last1=Meani|first1=Natalia|last2=Alcalay|first2=Myriam|title=Role of nucleophosmin in acute myeloid leukemia|journal=Expert Review of Anticancer Therapy|volume=9|issue=9|year=2014|pages=1283–1294|issn=1473-7140|doi=10.1586/era.09.84}}</ref> 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. 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.

==Interactions==
NPM1 has been shown to [[Protein-protein interaction|interact]] with 
* [[AKT1]],<ref name="pmid18931307">{{cite journal | vauthors = Lee SB, Xuan Nguyen TL, Choi JW, Lee KH, Cho SW, Liu Z, Ye K, Bae SS, Ahn JY | title = Nuclear Akt interacts with B23/NPM and protects it from proteolytic cleavage, enhancing cell survival | journal = Proc. Natl. Acad. Sci. U.S.A. | volume = 105 | issue = 43 | pages = 16584–9 |date=October 2008 | pmid = 18931307 | pmc = 2569968 | doi = 10.1073/pnas.0807668105 | url =  }}</ref>
* [[BARD1]],<ref name=pmid15184379/>
* [[BRCA1]],<ref name="pmid15184379">{{cite journal | vauthors = Sato K, Hayami R, Wu W, Nishikawa T, Nishikawa H, Okuda Y, Ogata H, Fukuda M, Ohta T | title = Nucleophosmin/B23 is a candidate substrate for the BRCA1-BARD1 ubiquitin ligase | journal = J. Biol. Chem. | volume = 279 | issue = 30 | pages = 30919–22 |date=July 2004 | pmid = 15184379 | doi = 10.1074/jbc.C400169200 | url =  }}</ref> and
* [[nucleolin]].<ref name="pmid8620867">{{cite journal | vauthors = Li YP, Busch RK, Valdez BC, Busch H | title = C23 interacts with B23, a putative nucleolar-localization-signal-binding protein | journal = Eur. J. Biochem. | volume = 237 | issue = 1 | pages = 153–8 |date=April 1996 | pmid = 8620867 | doi = 10.1111/j.1432-1033.1996.0153n.x | url =  }}</ref>

Nucleophosmin has multiple binding partners:<ref name="pmid21152184"/>
# 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

== References ==
{{Reflist}}

== Further reading ==
{{refbegin | 2}}
*{{cite journal   |vauthors=Yun C, Wang Y, Mukhopadhyay D, etal |title=Nucleolar protein B23/nucleophosmin regulates the vertebrate SUMO pathway through SENP3 and SENP5 proteases |journal=J. Cell Biol. |volume=183 |issue= 4 |pages= 589–95 |year= 2008 |pmid= 19015314 |doi=10.1083/jcb.200807185  | pmc=2582899 }}
*{{cite journal   |vauthors=Haindl M, Harasim T, Eick D, etal |title=The nucleolar SUMO-specific protease SENP3 reverses SUMO modification of nucleophosmin and is required for rRNA processing |journal=EMBO Reports |volume=9 |issue= 3 |pages= 273–279 |year= 2008  | pmid=18259216 |pmc= 2267381 |doi=10.1038/embor.2008.3 }}
*{{cite journal   |vauthors=Li L, Li HS, Pauza CD, etal |title=Roles of HIV-1 auxiliary proteins in viral pathogenesis and host-pathogen interactions |journal=Cell Res. |volume=15 |issue= 11–12 |pages= 923–34 |year= 2006 |pmid= 16354571 |doi= 10.1038/sj.cr.7290370 }}
*{{cite journal  | author=Gjerset RA |title=DNA damage, p14ARF, nucleophosmin (NPM/B23), and cancer |journal=J. Mol. Histol. |volume=37 |issue= 5–7 |pages= 239–51 |year= 2007 |pmid= 16855788 |doi= 10.1007/s10735-006-9040-y }}
*{{cite journal  | vauthors=Chen W, Rassidakis GZ, Medeiros LJ |title=Nucleophosmin gene mutations in acute myeloid leukemia |journal=Arch. Pathol. Lab. Med. |volume=130 |issue= 11 |pages= 1687–92 |year= 2006 |pmid= 17076533 |doi=  10.1043/1543-2165(2006)130[1687:NGMIAM]2.0.CO;2}}
*{{cite journal   |vauthors=Falini B, Nicoletti I, Bolli N, etal |title=Translocations and mutations involving the nucleophosmin (NPM1) gene in lymphomas and leukemias |journal=Haematologica |volume=92 |issue= 4 |pages= 519–32 |year= 2007 |pmid= 17488663 |doi=10.3324/haematol.11007  }}
*{{cite journal   |vauthors=Fankhauser C, Izaurralde E, Adachi Y, etal |title=Specific complex of human immunodeficiency virus type 1 rev and nucleolar B23 proteins: dissociation by the Rev response element |journal=Mol. Cell. Biol. |volume=11 |issue= 5 |pages= 2567–75 |year= 1991 |pmid= 2017166 |doi=  | pmc=360026  }}
*{{cite journal  | vauthors=Venkatesh LK, Mohammed S, Chinnadurai G |title=Functional domains of the HIV-1 rev gene required for trans-regulation and subcellular localization |journal=Virology |volume=176 |issue= 1 |pages= 39–47 |year= 1990 |pmid= 2109912 |doi=10.1016/0042-6822(90)90228-J  }}
*{{cite journal  | vauthors=Cochrane AW, Perkins A, Rosen CA |title=Identification of sequences important in the nucleolar localization of human immunodeficiency virus Rev: relevance of nucleolar localization to function |journal=J. Virol. |volume=64 |issue= 2 |pages= 881–5 |year= 1990 |pmid= 2404140 |doi=  | pmc=249184  }}
*{{cite journal   |vauthors=Chan PK, Chan WY, Yung BY, etal |title=Amino acid sequence of a specific antigenic peptide of protein B23 |journal=J. Biol. Chem. |volume=261 |issue= 30 |pages= 14335–41 |year= 1986 |pmid= 2429957 |doi=  }}
*{{cite journal  | vauthors=Zhang XX, Thomis DC, Samuel CE |title=Isolation and characterization of a molecular cDNA clone of a human mRNA from interferon-treated cells encoding nucleolar protein B23, numatrin |journal=Biochem. Biophys. Res. Commun. |volume=164 |issue= 1 |pages= 176–84 |year= 1989 |pmid= 2478125 |doi=10.1016/0006-291X(89)91699-9  }}
*{{cite journal  | vauthors=Hale TK, Mansfield BC |title=Nucleotide sequence of a cDNA clone representing a third allele of human protein B23 |journal=Nucleic Acids Res. |volume=17 |issue= 23 |pages= 10112 |year= 1990 |pmid= 2602120 |doi=  | pmc=335249  }}
*{{cite journal   |vauthors=Chan WY, Liu QR, Borjigin J, etal |title=Characterization of the cDNA encoding human nucleophosmin and studies of its role in normal and abnormal growth |journal=Biochemistry |volume=28 |issue= 3 |pages= 1033–9 |year= 1989 |pmid= 2713355 |doi=10.1021/bi00429a017  }}
*{{cite journal  | vauthors=Li XZ, McNeilage LJ, Whittingham S |title=The nucleotide sequence of a human cDNA encoding the highly conserved nucleolar phosphoprotein B23 |journal=Biochem. Biophys. Res. Commun. |volume=163 |issue= 1 |pages= 72–8 |year= 1989 |pmid= 2775293 |doi=10.1016/0006-291X(89)92100-1  }}
*{{cite journal  | vauthors=Chan PK, Aldrich M, Cook RG, Busch H |title=Amino acid sequence of protein B23 phosphorylation site |journal=J. Biol. Chem. |volume=261 |issue= 4 |pages= 1868–72 |year= 1986 |pmid= 3944116 |doi=  }}
*{{cite journal   |vauthors=Bocker T, Bittinger A, Wieland W, etal |title=In vitro and ex vivo expression of nucleolar proteins B23 and p120 in benign and malignant epithelial lesions of the prostate |journal=Mod. Pathol. |volume=8 |issue= 3 |pages= 226–31 |year= 1995 |pmid= 7542384 |doi=  }}
*{{cite journal   |vauthors=Dundr M, Leno GH, Hammarskjöld ML, etal |title=The roles of nucleolar structure and function in the subcellular location of the HIV-1 Rev protein |journal=J. Cell Sci. |volume=108 |issue=  8|pages= 2811–23 |year= 1995 |pmid= 7593322 |doi=  }}
*{{cite journal   |vauthors=Miyazaki Y, Takamatsu T, Nosaka T, etal |title=The cytotoxicity of human immunodeficiency virus type 1 Rev: implications for its interaction with the nucleolar protein B23 |journal=Exp. Cell Res. |volume=219 |issue= 1 |pages= 93–101 |year= 1995 |pmid= 7628555 |doi= 10.1006/excr.1995.1209 }}
*{{cite journal  | vauthors=Szebeni A, Herrera JE, Olson MO |title=Interaction of nucleolar protein B23 with peptides related to nuclear localization signals |journal=Biochemistry |volume=34 |issue= 25 |pages= 8037–42 |year= 1995 |pmid= 7794916 |doi=10.1021/bi00025a009  }}
*{{cite journal   |vauthors=Kato S, Sekine S, Oh SW, etal |title=Construction of a human full-length cDNA bank |journal=Gene |volume=150 |issue= 2 |pages= 243–50 |year= 1995 |pmid= 7821789 |doi=10.1016/0378-1119(94)90433-2  }}
*{{cite journal   |vauthors=Marasco WA, Szilvay AM, Kalland KH, etal |title=Spatial association of HIV-1 tat protein and the nucleolar transport protein B23 in stably transfected Jurkat T-cells |journal=Arch. Virol. |volume=139 |issue= 1–2 |pages= 133–54 |year= 1995 |pmid= 7826206 |doi=10.1007/BF01309460  }}
*{{cite journal   |vauthors=Valdez BC, Perlaky L, Henning D, etal |title=Identification of the nuclear and nucleolar localization signals of the protein p120. Interaction with translocation protein B23 |journal=J. Biol. Chem. |volume=269 |issue= 38 |pages= 23776–83 |year= 1994 |pmid= 8089149 |doi=  }}
{{refend}}

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[[Category:Genes on human chromosome 5]]