NPM1

NPM1
Available structures
PDBOrtholog search: PDBe RCSB
Identifiers
AliasesNPM1, B23, NPM, nucleophosmin (nucleolar phosphoprotein B23, numatrin), nucleophosmin, nucleophosmin 1
External IDsOMIM: 164040; MGI: 106184; HomoloGene: 81697; GeneCards: NPM1; OMA:NPM1 - orthologs
Orthologs
SpeciesHumanMouse
Entrez

4869

18148

Ensembl

ENSG00000181163

ENSMUSG00000057113

UniProt

P06748

Q61937

RefSeq (mRNA)

NM_001252260
NM_001252261
NM_008722

RefSeq (protein)

NP_001239189
NP_001239190
NP_032748

Location (UCSC)Chr 5: 171.39 – 171.41 MbChr 11: 33.1 – 33.11 Mb
PubMed search[3][4]
Wikidata
View/Edit HumanView/Edit Mouse

Nucleophosmin (NPM), also known as nucleolar phosphoprotein B23 or numatrin, is a protein that in humans is encoded by the NPM1 gene.[5][6]

Gene

[edit]

In humans, the NPM1 gene is located on the long arm of chromosome 5 (5q35). The gene spans 23 kb and contains 12 exons. Three transcript variants have been described. The longest isoform (294 amino acids long), encoded by transcript variant 1, is the major and the most well studied isoform of Nucleophosmin. Transcript variant 2 is produced by skipping an in-frame exon (exon 8) to produce an isoform that is 265 amino acids long. However, this isoform is not well characterized and its functions and expression pattern is not well understood. Transcript variant 3 is produced by using an alternate exon (exon 10) which results in an isoform 259 amino acids long with a different C-terminal sequence. The isoforms 1 and 3 of human NPM1 are B23.1 and B23.2 respectively in rat.[7] The isoform 1 is localized to the nucleolus[8] as is reported for rat B23.1[9][10] whereas the isoform 3 (B23.2) is nucleoplasmic or cytoplasmic in localization and is expressed at relatively lower levels as compared to isoform 1 in normal rat tissues[11] and in HeLa cells.[8] Both isoforms 1 and 3 have been shown to stimulate the replication of adenoviral DNA complexed with viral basic proteins.[8]

Function

[edit]

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. 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, but it can be translocated to the nucleoplasm in case of serum starvation or treatment with anticancer drugs. The protein was identified as a phosphoprotein. However, later other post-translational modifications for NPM1 were identified including acetylation and SUMOylation.

Nucleophosmin has multiple functions:[12]

  1. Histone chaperones
  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 when located in nucleolus

Molecular and histone chaperone

[edit]

NPM1 functions as a molecular chaperone for several proteins. Both the N-terminal hydrophobic core domain and acidic stretches are important for this activity. Furthermore, oligomerization of NPM1 has been shown to be necessary for maximum chaperone activity.[13] NPM1 has been predicted to play a role in preventing protein aggregation in the densely packed nucleolus especially during ribosome biogenesis. NPM1 shows characteristic properties of molecular chaperones such as a) preventing temperature dependent and independent aggregation of proteins, b) preserving enzyme activities during thermal denaturation of several different proteins, c) promoting the renaturation of previously denatured proteins, d) preferentially binding to denatured proteins, and exposing hydrophobic regions during interaction with other proteins. NPM1 can bind to ATP,[14] yet, its chaperoning function does not require ATP hydrolysis or the presence of ATP.[15]

NPM1 is known to associate with pre-ribosomal particles and other nucleolar proteins. Since ribosomal proteins tend to be insoluble under physiological conditions, NPM1 presumably binds to ribosomal proteins in the nucleolus, prevent them from aggregation and promote their assembly into the ribosomal subunits. Similarly, certain viral proteins such as HIV-1 Rev that are insoluble under physiological conditions, bind to NPM1 which prevents their aggregation and allows their accumulation in the nucleus/nucleolus thereby promoting viral particle assembly. Further, since NPM1 can shuttle between the nucleus and the cytoplasm[16] by virtue of its NES and NLS, it could help in co-translational folding of client proteins in the cytoplasm and promote their entry into the nucleus/nucleolus.[15]

NPM1 is a highly acidic protein and can bind to histones directly because of their basic nature. NPM1 binding to histones is retained even at a salt concentration of 0.5 M KCl suggesting a strong binding with the help of electrostatic interactions.[17] However, electrostatic interactions alone are not responsible for binding to histones as is suggested by the NPM1 core crystal structure. NPM1 directly binds to core histones H2B, H3 and H4 and can bind to H2A only in the presence of the H2A-H2B dimer or the core histone octamer. It can assemble nucleosomes in vitro and can decondense sperm chromatin similar to nucleoplasmin.[18][19][17] NPM1 histone chaperone activity has been suggested to be involved in nucleosome disassembly during transcription resulting in activation of transcription.[17] It is also presumed to function as a histone chaperone in the nucleolus.[20] Depletion of NPM1 or overexpression of a mutant NPM1 lacking histone chaperone activity leads to a decrease in rDNA transcription.[21] It can also bind to linker histone H1 and promote its assembly or disassembly from chromatin.[22]

Ribosome biogenesis

[edit]

NPM1 is a molecular chaperone.[15] It was also observed to associate with preribosomes, hence it was initially thought that NPM1 is a ribosome assembly factor or a ribosome chaperone.[23] Other characteristic properties that suggest NPM1 role in ribosome biogenesis are nucleolar localization, ability to shuttle between the nucleus and cytoplasm, ability to bind to nucleic acid and to transport pre-ribosomal particles.[16][24][25][26][27] NPM1 also has an intrinsic ribonuclease activity that cleaves a specific site in the ITS2 (Internal transcribed spacer 2) of the pre-5.8S rRNA.[28][29] Knockdown of NPM1 leads to changes in the profiles of ribosomes. (Grisendi et al., 2005) Degradation of NPM1 induced by ARF leads to defects in the processing of pre-ribosomal RNA from the 32S precursor rRNA to the 28S rRNA species (Itahana et al., 2003). Moreover, blocking the NPM1 nucleo-cytoplasmic shuttling inhibits ribosome subunit export resulting in a decrease in the cell growth rate showing that NPM1 exports pre-ribosomes (Maggi et al., 2008). Furthermore, NPM1 interacts with a number of ribosomal proteins including RPL5 (Yu et al., 2006), RPS9 (Lindström and Zhang, 2008) and RPL23 (Wanzel et al., 2008). NPM3 was shown to bind to NPM1 and negatively regulate ribosome biogenesis whereas an NPM1 binding defective mutant of NPM3 did not have any effect on ribosome biogenesis (Huang et al., 2001). Interestingly, NPM1 isoform 3 that does not have a nucleic acid binding domain also inhibits ribosome biogenesis. All these findings suggest an important role of NPM1 in ribosome biogenesis.

Most cancer cells have enlarged nucleoli and the aberrant overexpression of NPM1 has been correlated well with the increased ribosome biogenesis in highly proliferating cells. Thus NPM1 by controlling ribosome biogenesis could control the proliferative rate of cells. NPM1 knockout mouse embryos survive upto mid-gestation (9.5dpc-12.5dpc) (Colombo et al., 2005; Grisendi et al., 2005), whereas, knockout of pescadillo, a protein involved in ribosome biogenesis, leads to death of the embryos at morula stages (2.5 dpc) (Lerch-Gaggl et al., 2002). This suggests that either NPM1 may not be essential for ribosome biogenesis, as other proteins could have overlapping functions with NPM1 or there could be other factors such as ribosome storage in oocytes that could have compensated for the loss of NPM1 in NPM1 null embryos (Grisendi et al., 2006).

Role in Transcriptional regulation

[edit]

NPM1 has been shown to be an important co-activator for RNA Polymerase II driven transcription. Acetylation of NPM1 enhances this activity through increased histone binding and chaperone activity.[17] Intriguingly acetylated NPM1 (AcNPM1) is a distinct pool localized in the nucleoplasm in contrast to the nucleolar localization of unmodified and phosphorylated NPM1.[30] Genome-wide profiling of AcNPM1 occupancy by ChIP-sequencing reveals that it localizes to the transcription start site of many gene promoters and is co-occupied with RNA Polymerase II.[31]

Clinical significance

[edit]

The 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.[32] 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,[33] 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.[34]

In addition, NPM1 is overexpressed in many solid tumors including gastric, colon, breast, ovary, bladder, oral, thyroid, brain, liver, prostate cancer and multiple myeloma. NPM1 overexpression correlates well with the clinical features of hepatocellular carcinoma suggesting that NPM1 overexpression could serve as a diagnostic marker for hepatocellular carcinoma. NPM1 overexpression and hyperacetylation progresses according to the increasing grade of tumor in OSCC.[30] NPM1 overexpression also correlates well with recurrence and progression of bladder cancer to advanced stages. NPM1 overexpression is associated with acquired oestrogen-independence in human breast cancer cells (Skaar et al., 1998). Moreover, NPM1 is a direct transcriptional target of oncogenic transcription factor c-myc (Zeller et al., 2001). The ability of NPM1 to suppress apoptosis and promote DNA repair might be responsible for the survival of tumor cells where NPM1 is overexpressed. All these studies suggest that NPM1 overexpression promotes tumor development and hence could function as a proto-oncogene.

Discovery

[edit]

NPM1 was first discovered as a nucleolar phosphoprotein in rat liver cells and Novikoff hepatoma ascites cells.[35][36] It was named B23 as it was the 23rd spot in the B section of the 2-D gel where spots were numbered in the order of decreasing mobility. It was named numatrin independently by another group as it was found to be tightly associated with the nuclear matrix and its expression was induced upon mitogenic signals in human B lymphocytes.[37][38] At around the same time, the Xenopus NO38 was discovered and was found to be homologous to Xenopus Nucleoplasmin and rat B23.[39]

Structure

[edit]

The NPM1 protein can be divided into several domains with sequence motifs that are conserved across nucleoplasmin family and have important and distinct functions. The N-terminal core domain, the acidic stretches, basic domain and the aromatic nucleic acid domain make up the NPM1 protein. Further, sequence motifs such as the nuclear export signals (NES), nuclear localization signals (NLS) and the nucleolar localization signals (NoLS) are critical for the localization of NPM1 to the nucleolus as well as its nucleo-cytoplasmic shuttling required for its diverse array of functions.

The N-terminal domain also known as the core domain (residues 1-119 of human NPM1) is the most conserved domain among the NPM family proteins. This domain folds into a distinct structure that is protease resistant and is responsible for the oligomerization and chaperone activity of these proteins. It contains several hydrophobic residues that are highly conserved (~80%) among NPM proteins. The crystal structure of NPM1 core domain (residues 9-122) shows that this domain folds into an eight stranded β-barrel with jelly roll topology forming a wedge shaped hydrophobic core that fits snugly to form a pentamer through hydrophobic interactions between the monomeric subunits. Two pentameric complexes align in a head to head fashion to form the decameric structure. A comparison between the crystal structure of human NPM1 and that of the core domains of Xenopus NO38, Xenopus Nucleoplasmin and Drosophila Nucleoplasmin like protein (dNLP) show that both the monomeric and pentameric structures are highly similar among all the NPM family proteins. The human NPM1 core domain (residues 15-118) shares a sequence identity of 80%, 51% and 29% with Xenopus NO38, Nucleoplasmin and Drosophila NLP cores respectively. All of them form the same β barrel structure with jelly roll topology.

NPM1 was speculated to be a hexamer under native conditions since it was found to have a molecular weight of 230–255 kDa calculated by gel filtration chromatography and sedimentation analyses. However, the crystal structure of the NPM1 core clearly shows that it is a pentamer. The pentamer-pentamer interface consists of several water molecules involved in hydrogen bonding between the two pentamers. Moreover, ten charge based interactions between the Asp of the highly conserved AKDE loop and Lys82 give additional stability. Comparison of dNLP and Nucleoplasmin structures has revealed that formation of the decamer might be facilitated by histone binding. The H2A-H2B dimer may bind to the lateral surface of the NPM1 decamer. Furthermore, comparison of the crystal structures of human NPM1 and Xenopus NO38 reveals structural plasticity in the pentamer-pentamer interface. When one of the pentamers of human NPM1 and Xenopus NO38 are superimposed, there is a large rotational offset (~20°) between the other pentamers. Further, the direction of the rotational offsets are opposite for human NPM1 and Xenopus NO38 when compared to Xenopus Nucleoplasmin core structure. The significance of this structural plasticity is not well understood, however, it may have a significance in the chaperone function of NPM1.

Interactions

[edit]

NPM1 has been shown to interact with

Nucleophosmin has multiple binding partners:[12]

  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

[edit]
  1. ^ a b c GRCh38: Ensembl release 89: ENSG00000181163 – Ensembl, May 2017
  2. ^ a b c GRCm38: Ensembl release 89: ENSMUSG00000057113 – Ensembl, May 2017
  3. ^ "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  4. ^ "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  5. ^ Liu QR, Chan PK (March 1993). "Characterization of seven processed pseudogenes of nucleophosmin/B23 in the human genome". DNA and Cell Biology. 12 (2): 149–156. doi:10.1089/dna.1993.12.149. PMID 8471164.
  6. ^ 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): 1281–1284. Bibcode:1994Sci...263.1281M. doi:10.1126/science.8122112. PMID 8122112.
  7. ^ Chang JH, Olson MO (July 1989). "A single gene codes for two forms of rat nucleolar protein B23 mRNA". The Journal of Biological Chemistry. 264 (20): 11732–11737. doi:10.1016/S0021-9258(18)80126-0. PMID 2745414.
  8. ^ a b c Okuwaki M, Iwamatsu A, Tsujimoto M, Nagata K (August 2001). "Identification of nucleophosmin/B23, an acidic nucleolar protein, as a stimulatory factor for in vitro replication of adenovirus DNA complexed with viral basic core proteins". Journal of Molecular Biology. 311 (1): 41–55. doi:10.1006/jmbi.2001.4812. PMID 11469856.
  9. ^ Michalik J, Yeoman LC, Busch H (March 1981). "Nucleolar localization of protein B23 (37/5.1) by immunocytochemical techniques". Life Sciences. 28 (12): 1371–1379. doi:10.1016/0024-3205(81)90411-2. PMID 7017325.
  10. ^ Spector DL, Ochs RL, Busch H (1984). "Silver staining, immunofluorescence, and immunoelectron microscopic localization of nucleolar phosphoproteins B23 and C23". Chromosoma. 90 (2): 139–148. doi:10.1007/BF00292451. PMID 6206987. S2CID 38080472.
  11. ^ Wang D, Umekawa H, Olson MO (1993). "Expression and subcellular locations of two forms of nucleolar protein B23 in rat tissues and cells". Cellular & Molecular Biology Research. 39 (1): 33–42. PMID 8287070.
  12. ^ a b Lindström MS (2011). "NPM1/B23: A Multifunctional Chaperone in Ribosome Biogenesis and Chromatin Remodeling". Biochemistry Research International. 2011: 195209. doi:10.1155/2011/195209. PMC 2989734. PMID 21152184.
  13. ^ Hingorani K, Szebeni A, Olson MO (August 2000). "Mapping the functional domains of nucleolar protein B23". The Journal of Biological Chemistry. 275 (32): 24451–24457. doi:10.1074/jbc.M003278200. PMID 10829026.
  14. ^ Chang JH, Lin JY, Wu MH, Yung BY (February 1998). "Evidence for the ability of nucleophosmin/B23 to bind ATP". The Biochemical Journal. 329 ( Pt 3) (Pt 3): 539–544. doi:10.1042/bj3290539. PMC 1219074. PMID 9445380.
  15. ^ a b c Szebeni A, Olson MO (April 1999). "Nucleolar protein B23 has molecular chaperone activities". Protein Science. 8 (4): 905–912. doi:10.1110/ps.8.4.905. PMC 2144306. PMID 10211837.
  16. ^ a b Borer RA, Lehner CF, Eppenberger HM, Nigg EA (February 1989). "Major nucleolar proteins shuttle between nucleus and cytoplasm". Cell. 56 (3): 379–390. doi:10.1016/0092-8674(89)90241-9. PMID 2914325. S2CID 32557569.
  17. ^ a b c d Swaminathan V, Kishore AH, Febitha KK, Kundu TK (September 2005). "Human histone chaperone nucleophosmin enhances acetylation-dependent chromatin transcription". Molecular and Cellular Biology. 25 (17): 7534–7545. doi:10.1128/MCB.25.17.7534-7545.2005. PMC 1190275. PMID 16107701.
  18. ^ Okuwaki, M.; Iwamatsu, A.; Tsujimoto, M.; Nagata, K. (2001-08-03). "Identification of nucleophosmin/B23, an acidic nucleolar protein, as a stimulatory factor for in vitro replication of adenovirus DNA complexed with viral basic core proteins". Journal of Molecular Biology. 311 (1): 41–55. doi:10.1006/jmbi.2001.4812. ISSN 0022-2836. PMID 11469856.
  19. ^ Okuwaki, M.; Matsumoto, K.; Tsujimoto, M.; Nagata, K. (2001-10-12). "Function of nucleophosmin/B23, a nucleolar acidic protein, as a histone chaperone". FEBS Letters. 506 (3): 272–276. doi:10.1016/s0014-5793(01)02939-8. ISSN 0014-5793. PMID 11602260. S2CID 27961615.
  20. ^ Namboodiri, V. M. Haridasan; Akey, Ildikó V.; Schmidt-Zachmann, Marion S.; Head, James F.; Akey, Christopher W. (December 2004). "The structure and function of Xenopus NO38-core, a histone chaperone in the nucleolus". Structure. 12 (12): 2149–2160. doi:10.1016/j.str.2004.09.017. ISSN 0969-2126. PMID 15576029.
  21. ^ Murano, Kensaku; Okuwaki, Mitsuru; Hisaoka, Miharu; Nagata, Kyosuke (May 2008). "Transcription regulation of the rRNA gene by a multifunctional nucleolar protein, B23/nucleophosmin, through its histone chaperone activity". Molecular and Cellular Biology. 28 (10): 3114–3126. doi:10.1128/MCB.02078-07. ISSN 1098-5549. PMC 2423177. PMID 18332108.
  22. ^ a b Gadad, Shrikanth S.; Senapati, Parijat; Syed, Sajad Hussain; Rajan, Roshan Elizabeth; Shandilya, Jayasha; Swaminathan, Venkatesh; Chatterjee, Snehajyoti; Colombo, Emanuela; Dimitrov, Stefan; Pelicci, Pier Giuseppe; Ranga, Udaykumar; Kundu, Tapas K. (2011-04-12). "The multifunctional protein nucleophosmin (NPM1) is a human linker histone H1 chaperone". Biochemistry. 50 (14): 2780–2789. doi:10.1021/bi101835j. ISSN 1520-4995. PMID 21425800.
  23. ^ Yu Y, Maggi LB, Brady SN, Apicelli AJ, Dai MS, Lu H, Weber JD (May 2006). "Nucleophosmin is essential for ribosomal protein L5 nuclear export". Molecular and Cellular Biology. 26 (10): 3798–3809. doi:10.1128/MCB.26.10.3798-3809.2006. PMC 1488996. PMID 16648475.
  24. ^ Dumbar TS, Gentry GA, Olson MO (November 1989). "Interaction of nucleolar phosphoprotein B23 with nucleic acids". Biochemistry. 28 (24): 9495–9501. doi:10.1021/bi00450a037. PMID 2482073.
  25. ^ Olson, M. O.; Wallace, M. O.; Herrera, A. H.; Marshall-Carlson, L.; Hunt, R. C. (1986-01-28). "Preribosomal ribonucleoprotein particles are a major component of a nucleolar matrix fraction". Biochemistry. 25 (2): 484–491. doi:10.1021/bi00350a031. ISSN 0006-2960. PMID 3955008.
  26. ^ Wang, D.; Baumann, A.; Szebeni, A.; Olson, M. O. (1994-12-09). "The nucleic acid binding activity of nucleolar protein B23.1 resides in its carboxyl-terminal end". The Journal of Biological Chemistry. 269 (49): 30994–30998. doi:10.1016/S0021-9258(18)47380-2. ISSN 0021-9258. PMID 7527039.
  27. ^ Yun, Jing-Ping; Chew, Eng Ching; Liew, Choong-Tsek; Chan, John Y. H.; Jin, Mei-Lin; Ding, Ming-Xiao; Fai, Yam Hin; Li, H. K. Richard; Liang, Xiao-Man; Wu, Qiu-Liang (2003-12-15). "Nucleophosmin/B23 is a proliferate shuttle protein associated with nuclear matrix". Journal of Cellular Biochemistry. 90 (6): 1140–1148. doi:10.1002/jcb.10706. ISSN 0730-2312. PMID 14635188.
  28. ^ Herrera, J. E.; Savkur, R.; Olson, M. O. (1995-10-11). "The ribonuclease activity of nucleolar protein B23". Nucleic Acids Research. 23 (19): 3974–3979. doi:10.1093/nar/23.19.3974. ISSN 0305-1048. PMC 307319. PMID 7479045.
  29. ^ Savkur, R. S.; Olson, M. O. (1998-10-01). "Preferential cleavage in pre-ribosomal RNA byprotein B23 endoribonuclease". Nucleic Acids Research. 26 (19): 4508–4515. doi:10.1093/nar/26.19.4508. ISSN 0305-1048. PMC 147876. PMID 9742256.
  30. ^ a b Shandilya J, Swaminathan V, Gadad SS, Choudhari R, Kodaganur GS, Kundu TK (September 2009). "Acetylated NPM1 localizes in the nucleoplasm and regulates transcriptional activation of genes implicated in oral cancer manifestation". Molecular and Cellular Biology. 29 (18): 5115–5127. doi:10.1128/MCB.01969-08. PMC 2738287. PMID 19581289.
  31. ^ Senapati P, Bhattacharya A, Das S, Dey S, Sudarshan D, G S, et al. (February 2022). "Histone Chaperone Nucleophosmin Regulates Transcription of Key Genes Involved in Oral Tumorigenesis". Molecular and Cellular Biology. 42 (2): e0066920. doi:10.1128/mcb.00669-20. PMC 8852714. PMID 34898280.
  32. ^ Falini B, Nicoletti I, Bolli N, Martelli MP, Liso A, Gorello P, et al. (April 2007). "Translocations and mutations involving the nucleophosmin (NPM1) gene in lymphomas and leukemias". Haematologica. 92 (4): 519–532. doi:10.3324/haematol.11007. hdl:2434/424144. PMID 17488663.
  33. ^ Meani N, Alcalay M (September 2009). "Role of nucleophosmin in acute myeloid leukemia". Expert Review of Anticancer Therapy. 9 (9): 1283–1294. doi:10.1586/era.09.84. PMID 19761432. S2CID 7390794.
  34. ^ Loberg MA, Bell RK, Goodwin LO, Eudy E, Miles LA, SanMiguel JM, et al. (July 2019). "Sequentially inducible mouse models reveal that Npm1 mutation causes malignant transformation of Dnmt3a-mutant clonal hematopoiesis". Leukemia. 33 (7): 1635–1649. doi:10.1038/s41375-018-0368-6. PMC 6609470. PMID 30692594.
  35. ^ Olson MO, Orrick LR, Jones C, Busch H (May 1974). "Phosphorylation of acid-soluble nucleolar proteins of Novikoff hepatoma ascites cells in vivo". The Journal of Biological Chemistry. 249 (9): 2823–2827. doi:10.1016/S0021-9258(19)42704-X. PMID 4364031.
  36. ^ Orrick LR, Olson MO, Busch H (May 1973). "Comparison of nucleolar proteins of normal rat liver and Novikoff hepatoma ascites cells by two-dimensional polyacrylamide gel electrophoresis". Proceedings of the National Academy of Sciences of the United States of America. 70 (5): 1316–1320. Bibcode:1973PNAS...70.1316O. doi:10.1073/pnas.70.5.1316. PMC 433487. PMID 4351171.
  37. ^ Feuerstein N, Chan PK, Mond JJ (August 1988). "Identification of numatrin, the nuclear matrix protein associated with induction of mitogenesis, as the nucleolar protein B23. Implication for the role of the nucleolus in early transduction of mitogenic signals". The Journal of Biological Chemistry. 263 (22): 10608–10612. doi:10.1016/S0021-9258(18)38014-1. PMID 3392030.
  38. ^ Feuerstein N, Mond JJ (August 1987). ""Numatrin," a nuclear matrix protein associated with induction of proliferation in B lymphocytes". The Journal of Biological Chemistry. 262 (23): 11389–11397. doi:10.1016/S0021-9258(18)60972-X. PMID 3301855.
  39. ^ Schmidt-Zachmann MS, Hügle-Dörr B, Franke WW (July 1987). "A constitutive nucleolar protein identified as a member of the nucleoplasmin family". The EMBO Journal. 6 (7): 1881–1890. doi:10.1002/j.1460-2075.1987.tb02447.x. PMC 553572. PMID 3308448.
  40. ^ Lee SB, Xuan Nguyen TL, Choi JW, Lee KH, Cho SW, Liu Z, et al. (October 2008). "Nuclear Akt interacts with B23/NPM and protects it from proteolytic cleavage, enhancing cell survival". Proceedings of the National Academy of Sciences of the United States of America. 105 (43): 16584–16589. Bibcode:2008PNAS..10516584L. doi:10.1073/pnas.0807668105. PMC 2569968. PMID 18931307.
  41. ^ a b Sato K, Hayami R, Wu W, Nishikawa T, Nishikawa H, Okuda Y, et al. (July 2004). "Nucleophosmin/B23 is a candidate substrate for the BRCA1-BARD1 ubiquitin ligase". The Journal of Biological Chemistry. 279 (30): 30919–30922. doi:10.1074/jbc.C400169200. PMID 15184379. S2CID 23001611.
  42. ^ Li YP, Busch RK, Valdez BC, Busch H (April 1996). "C23 interacts with B23, a putative nucleolar-localization-signal-binding protein". European Journal of Biochemistry. 237 (1): 153–158. doi:10.1111/j.1432-1033.1996.0153n.x. PMID 8620867.

Further reading

[edit]
Retrieved from "https://en.wikipedia.org/w/index.php?title=NPM1&oldid=1218029615"