Molecule Information

General Information of the Molecule (ID: Mol01853)

• Name: Nucleophosmin (NPM1) ,Homo sapiens
• Synonyms: Nucleophosmin; NPM; Nucleolar phosphoprotein B23; Nucleolar protein NO38; Numatrin
• Molecule Type: Protein
• Gene Name: NPM1
• Gene ID: 4869
• Location: chr5:171,387,116-171,411,810[+]
• Sequence:
  MEDSMDMDMSPLRPQNYLFGCELKADKDYHFKVDNDENEHQLSLRTVSLGAGAKDELHIV
  EAEAMNYEGSPIKVTLATLKMSVQPTVSLGGFEITPPVVLRLKCGSGPVHISGQHLVAVE
  EDAESEDEEEEDVKLLSISGKRSAPGGGSKVPQKKVKLAADEDDDDDDEEDDDEDDDDDD
  FDDEEAEEKAPVKKSIRDTPAKNAQKSNQNGKDSKPSSTPRSKGQESFKKQEKTPKTPKG
  PSSVEDIKAKMQASIEKGGSLPKVEAKFINYVKNCFRMTDQEAIQDLWQWRKSL
• Function: Involved in diverse cellular processes such as ribosome biogenesis, centrosome duplication, protein chaperoning, histone assembly, cell proliferation, and regulation of tumor suppressors p53/TP53 and ARF. Binds ribosome presumably to drive ribosome nuclear export. Associated with nucleolar ribonucleoprotein structures and bind single-stranded nucleic acids. Acts as a chaperonin for the core histones H3, H2B and H4. Stimulates APEX1 endonuclease activity on apurinic/apyrimidinic (AP) double-stranded DNA but inhibits APEX1 endonuclease activity on AP single-stranded RNA. May exert a control of APEX1 endonuclease activity within nucleoli devoted to repair AP on rDNA and the removal of oxidized rRNA molecules. In concert with BRCA2, regulates centrosome duplication. Regulates centriole duplication: phosphorylation by PLK2 is able to trigger centriole replication. Negatively regulates the activation of EIF2AK2/PKR and suppresses apoptosis through inhibition of EIF2AK2/PKR autophosphorylation. Antagonizes the inhibitory effect of ATF5 on cell proliferation and relieves ATF5-induced G2/M blockade. In complex with MYC enhances the transcription of MYC target genes.
• Uniprot ID: NPM_HUMAN
• Ensembl ID: ENSG00000181163
• HGNC ID: HGNC:7910

Kingdom: Metazoa
Phylum: Chordata
Class: Mammalia
Order: Primates
Family: Hominidae
Genus: Homo
Species: Homo sapiens

Type(s) of Resistant Mechanism of This Molecule

  ADTT: Aberration of the Drug's Therapeutic Target

  UAPP: Unusual Activation of Pro-survival Pathway

Drug Resistance Data Categorized by Drug

Preclinical Drug(s) 1 drug(s) in total

NSC348884

Drug Sensitivity Data Categorized by Their Corresponding Mechanisms

Aberration of the Drug's Therapeutic Target (ADTT)

Disease Class: Acute myeloid leukemia [1]

• Sensitive Disease: Acute myeloid leukemia [ICD-11: 2A60.0]
• Sensitive Drug: NSC348884
• Molecule Alteration: FS-deletion; p.W288fs (c.863_864)
• Experimental Note: Revealed Based on the Cell Line Data
• In Vitro Model: OCI-AML3 cells; Blood; Homo sapiens (Human); CVCL_1844
• In Vitro Model: HL-60 cells; Peripheral blood; Homo sapiens (Human); CVCL_0002
• Experiment for Molecule Alteration: Immunoblotting analysis
• Experiment for Drug Resistance: Colony-forming assay
• Mechanism Description: The fs-deletion p.W288fs (c.863_864) in gene NPM1 cause the sensitivity of NSC348884 by aberration of the drug's therapeutic target.

Investigative Drug(s) 1 drug(s) in total

Induction therapy

Drug Sensitivity Data Categorized by Their Corresponding Mechanisms

Unusual Activation of Pro-survival Pathway (UAPP)

Disease Class: Acute myeloid leukemia [2]

• Sensitive Disease: Acute myeloid leukemia [ICD-11: 2A60.0]
• Sensitive Drug: Induction therapy
• Molecule Alteration: FS-deletion; p.W288fs (c.863_864)
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: Bone marrow; .
• Experiment for Molecule Alteration: Immunostaining assay
• Mechanism Description: The fs-deletion p.W288fs (c.863_864) in gene NPM1 cause the sensitivity of Induction Therapy by unusual activation of pro-survival pathway.

Disease- and Tissue-specific Abundances of This Molecule

ICD Disease Classification 02

Acute myeloid leukemia [ICD-11: 2A60]

Differential expression of molecule in resistant diseases

• The Studied Tissue: Bone marrow
• The Specified Disease: Acute myeloid leukemia
• The Expression Level of Disease Section Compare with the Healthy Individual Tissue: p-value: 1.60E-40; Fold-change: 6.26E-01; Z-score: 2.03E+00

References

• Ref 1: Targeting levels or oligomerization of nucleophosmin 1 induces differentiation and loss of survival of human AML cells with mutant NPM1Blood. 2011 Sep 15;118(11):3096-106. doi: 10.1182/blood-2010-09-309674. Epub 2011 Jun 30.
• Ref 2: Cytoplasmic nucleophosmin in acute myelogenous leukemia with a normal karyotypeN Engl J Med. 2005 Jan 20;352(3):254-66. doi: 10.1056/NEJMoa041974.