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Nucleophosmin in leukemia: Consequences of anchor loss

Publikace na Ústřední knihovna |
2019

Tento text není v aktuálním jazyce dostupný. Zobrazuje se verze "en".Abstrakt

Nucleophosmin (NPM), one of the most abundant nucleolar proteins, has crucial functions in ribosome bio-genesis, cell cycle control, and DNA-damage repair. In human cells, NPM occurs mainly in oligomers.

It functions as a chaperone, undergoes numerous interactions and forms part of many protein complexes. Although NPM role in carcinogenesis is not fully elucidated, a variety of tumor suppressor as well as oncogenic activities were described.

NPM is overexpressed, fused with other proteins, or mutated in various tumor types. In the acute myeloid leukemia (AML), characteristic mutations in NPM1 gene, leading to modification of NPM C-terminus, are the most frequent genetic aberration.

Although multiple mutation types of NPM are found in AML, they are all characterized by aberrant cytoplasmic localization of the mutated protein. In this review, current knowledge of the structure and function of NPM is presented in relation to its interaction network, in particular to the interaction with other nucleolar proteins and with proteins active in apoptosis.

Possible molecular mechanisms of NPM mutation-driven leukemogenesis and NPM therapeutic targeting are discussed. Finally, recent findings concerning the immunogenicity of the mutated NPM and specific immunological features of AML patients with NPM mutation are summarized.