nucleophosmin

Nucleophosmin, also known as NPM1 or B23, is a widely expressed, predominantly nucleolar phosphoprotein in human cells. It is encoded by the NPM1 gene on chromosome 5q35 and belongs to the nucleophosmin/nucleoplasmin family. Nucleophosmin shuttles between the nucleolus, nucleus, and cytoplasm and participates in ribosome biogenesis, stress responses, and centrosome duplication. It acts as a molecular chaperone that binds and escorts ribosomal proteins and participates in preribosome assembly, ribosomal RNA processing, and export of ribosomal subunits.

Structurally, NPM1 forms homopentamers and contains an N-terminal oligomerization domain, a central acidic region that contributes to nucleolar localization, and a C-terminal domain with RNA- and ribosome-binding capabilities. The protein's localization is governed by nuclear localization and export signals, and its compartmental cycling is regulated by post-translational modifications such as phosphorylation during the cell cycle.

In addition to its role in ribosome production, NPM1 interacts with the p53 tumor suppressor pathway. It binds ARF and ribosomal proteins such as RPL5 and RPL11, aiding stabilization of p53 in response to nucleolar stress. It also participates in centrosome duplication and genomic stability.

Clinical significance: NPM1 is frequently altered in cancer. The most common disease association is acute myeloid leukemia (AML) with NPM1 mutations that create a cytoplasmic mutant form (NPM1c) due to acquisition of a novel C-terminal nuclear export signal and loss of nucleolar localization. NPM1 mutations serve as a diagnostic marker and have prognostic implications, especially in AML as part of risk stratification. Beyond leukemia, aberrant NPM1 expression has been observed in various solid tumors, reflecting its role in cell growth and survival.

Nucleophosmin is studied as a potential therapeutic target and biomarker, with ongoing research into its regulatory networks and interactions in ribosome biology and cancer.