B23nucleophosmin

B23 nucleophosmin, commonly referred to as nucleophosmin or NPM1, is a ubiquitously expressed, acidic nucleolar phosphoprotein that plays essential roles in ribosome biogenesis and cellular stress responses. The protein is encoded by the NPM1 gene on chromosome 5q35 and belongs to the nucleophosmin/nucleoplasmin family. In normal cells it localizes primarily to the nucleolus but can shuttle to the nucleoplasm and cytoplasm in response to cellular stress or during certain cell cycle stages.

NPM1 has a modular structure with an N-terminal oligomerization domain that promotes pentamer formation, a central acidic region that binds ribosomal proteins, and a C-terminal domain containing a nucleolar localization signal and a pair of conserved tryptophan residues important for RNA binding and nucleolar accumulation. This architecture supports its role as a molecular chaperone during ribosome assembly and as a regulator of ribosomal RNA processing.

Functionally, NPM1 participates in ribosome biogenesis by docking ribosomal proteins to ribosomal RNA and facilitating ribosome export to the cytoplasm. It also contributes to centrosome duplication, genome stability, and the regulation of cell cycle progression. Through interactions with the p53/MDM2 pathway via the ARF tumor suppressor, NPM1 influences cellular stress responses and apoptosis.

Clinical relevance is highlighted by the frequent NPM1 mutations observed in acute myeloid leukemia (AML). Many AML-associated mutations alter the C-terminus and create a new nuclear export signal, causing cytoplasmic accumulation of NPM1 (often termed NPM1c+). This mislocalization serves as a diagnostic marker and has prognostic and therapeutic implications, while broader defects in NPM1 function are linked to disorders of ribosome biogenesis and aging.