Recombinant Human NPM1 protein

NPM1 (Nucleophosmin 1) is a multifunctional nucleolar protein encoded by the *NPM1* gene located on chromosome 5q35. It plays critical roles in ribosome biogenesis, centrosome duplication, cell cycle regulation, and stress response. Structurally, NPM1 contains a conserved N-terminal oligomerization domain, a central histone-binding region, and a C-terminal nucleic acid-binding domain. Under physiological conditions, NPM1 shuttles between the nucleolus and nucleoplasm, maintaining genomic stability and regulating apoptosis.

In hematological malignancies, particularly acute myeloid leukemia (AML), recurrent *NPM1* mutations (commonly exon 12 frameshifts) result in cytoplasmic mislocalization of the mutant protein (NPM1c+). These mutations create a novel nuclear export signal and disrupt nucleolar localization signals, causing aberrant accumulation in the cytoplasm. This mislocalization is recognized as a key driver of leukemogenesis, often cooperating with other genetic alterations like *FLT3*-ITD. NPM1 mutations occur in approximately 30% of AML cases and define a distinct WHO classification category.

Recombinant NPM1 proteins, produced through bacterial (e.g., *E. coli*) or eukaryotic expression systems, are essential tools for studying these mechanisms. They enable biochemical characterization of mutant vs. wild-type protein interactions, particularly with binding partners like ARF, p53. and chromatin. Researchers use recombinant NPM1 to investigate structural consequences of mutations, develop targeted therapies (e.g., nuclear export inhibitors), and create diagnostic assays. Recent applications include CRISPR-based correction studies and drug screening platforms to identify compounds that reverse NPM1c+ mislocalization. The protein's chaperone-like properties and role in liquid-liquid phase separation also make it relevant to broader cancer and neurodegenerative disease research.