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→Gene Overview
==Gene Overview==
==Gene Overview==
* ''NPM1' encodes for nucleophosmin and belongs to the nucleophosmin/nucleoplasmin family of proteins [1]. The protein shuttles between the nucleolus, nucleus and cytoplasm, though it primarily stays in the nucleolus; in normal conditions, nuclear import of ''NPM1'' predominates over export, and ''NPM1'' is predominantly functionally active in the nucleolus. In the maintenance of genomic stability, ''NPM1'' binds unduplicated centrosomes in the cytoplasm to prevent duplication, and dissociates to allow duplication; in this way, ''NPM1'' acts as a licensing system for centrosome duplication by facilitating coordination with DNA replication and restricting centrosome duplication to once per cell cycle [2]. The N-terminal domain contains two nuclear export signal motifs. The central region contains two acidic regions spanning a bipartite nuclear localization signal. The C-terminal domain contains both the nuclear localization signal and the nucleolar localization signal [3,4]. See Figure 1 in [4].
* In ribosome biogenesis, ''NPM1'' facilitates the export of pre-ribosomal proteins from the nucleus for incorporation into ribosomal subunits in the cytoplasms; as a chaperone, it coordinates the assembly of the large number of proteins required for ribosome biogenesis [3,4]. NPM1 also has histone chaperone function [4].
* ''NPM1'' has a crucial role in modulating stress response and growth suppression by stabilizing p53 in the nucleus, as well as inhibiting MDM2 (mouse double minute 2 homolog) (a p53 E3-ubiquitin ligase that causes inactivation of p53), ultimately contributing to growth arrest [5,6]. ''NPM1'' prevents degradation of Arf (Alternate reading frame protein). As a tumor suppressor, ''Arf'' suppresses cell growth by disrupting ribosomal RNA precursor processing and suppressing ribosome biogenesis [7]; ''Arf'' also localizes ''MDM2'' to the nucleolus and therefore inhibits ''MDM2'', consequently relieving p53 inhibition. [8]. ''NPM1'' controls the transcriptional activity of Myc at target gene promoters and influences Myc suppression by facilitating degradation of Myc [9]; ''NPM1'' is required to localize and stabilize Fbw7γ (an F-box protein component to the E3 ubiquitin ligase complex) which promotes Myc degradation. See Figure 2 in [4].
* In the cytoplasm, NPM1 inhibits the activated forms of caspase-6 and -8 and reduces caspase-induced apoptosis/cell death [10].
==Common Alteration Types==
==Common Alteration Types==