NPM1

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

Function
NPM1 is associated with nucleolar is_associated_with::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 is_associated_with::ribosomes and may assist small basic proteins in their transport to the is_associated_with::nucleolus. Its regulation through SUMOylation (by is_associated_with::SENP3 and is_associated_with::SENP5) is another facet of the proteins's regulation and cellular functions.

It is located in the is_associated_with::nucleolus, but it can be translocated to the is_associated_with::nucleoplasm in case of serum starvation or treatment with anticancer drugs. The protein is is_associated_with::phosphorylated.

Nucleophosmin has multiple functions:
 * 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 when located in nucleolus

Clinical significance
NPM1 gene is up-regulated, mutated and chromosomally translocated in many tumor types. is_associated_with::Chromosomal aberrations involving NPM1 were found in patients with is_associated_with::non-Hodgkin lymphoma, is_associated_with::acute promyelocytic leukemia, is_associated_with::myelodysplastic syndrome, and is_associated_with::acute myelogenous leukemia. 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 is_associated_with::acute myelogenous leukemia, 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 farmalogical chaperones and the displacemet of the protein from nucleolus to nucleoplasm, which has been linked to apoptotic mechanisms.

Interactions
NPM1 has been shown to interact with
 * is_associated_with::AKT1,
 * is_associated_with::BARD1,
 * is_associated_with::BRCA1, and
 * is_associated_with::nucleolin.

Nucleophosmin has multiple binding partners:
 * 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