Nucleophosmin (NPM) is a nucleolar phosphoprotein that shuttles between the nucleus and cytoplasm during the cell cycle. NPM has several interacting partners and diverse cellular functions, including the processing of ribosomal RNA, centrosome duplication and the control of cellular processes to ensure genomic stability. Subcellular localization of NPM appears to be strongly correlated with NPM functions and cell proliferation. NPM is phosphorylated mainly at its central acidic domain by several upstream kinases, and its phosphorylation appears to be involved in regulating its functions in ribosome biogenesis and centrosome duplication. Recent studies suggest that NPM may act as a licensing factor to maintain proper centrosome duplication and that the Ran/CRM1 nucleocytoplasmic complex regulates local trafficking of NPM to centrosomes by interacting through its nuclear export sequence motif. Here, we provide a brief overview of NPM functions and its roles in human carcinogenesis, and discuss our recent findings related to the potential mechanisms underlying its regulation of centrosome duplication.
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http://dx.doi.org/10.1016/j.cdp.2006.10.008 | DOI Listing |
Leukemia
December 2024
Institute of Hematology and Center for Hemato-Oncological research (CREO), University of Perugia and Santa Maria della Misericordia Hospital, Perugia, Italy.
The nucleophosmin (NPM1) gene encodes for the most abundant nucleolar protein. Thanks to its property to act as histone chaperone and to shuttle between the nucleus and cytoplasm, the NPM1 protein is involved in multiple cellular function that are here extensively reviewed and include the formation of the nucleolus through liquid-liquid phase separation, regulation of ribosome biogenesis and transport, control of DNA repair and centrosome duplication as well as response to nucleolar stress. NPM1 is mutated in about 30-35% of adult acute myeloid leukemia (AML).
View Article and Find Full Text PDFMethods Mol Biol
December 2024
Graduate School of Life Science, Hokkaido University, Sapporo, Japan.
Drastic changes in chromosome number and cellular contents upon ploidy alterations profoundly affect the stability of mitotic regulation in different biological and pathological processes. Isogenic ploidy series of somatic cell lines are useful for studying the effects of ploidy differences on mitotic regulation at cellular and molecular levels. This chapter describes experimental procedures using isogenic human HAP1 cell lines that cover haploid, diploid, and tetraploid states.
View Article and Find Full Text PDFbioRxiv
October 2024
Division of Biology and Biological Engineering, California Institute of Technology, Pasadena, California 91125, USA.
The conserved process of centriole duplication requires establishment of a Sas6-centred cartwheel initiated by Plk4's phosphorylation of Ana1/STIL. Subsequently the centriole undergoes conversion to a centrosome requiring its radial expansion and elongation, mediated by a network requiring interactions between Cep135, Ana1/Cep295, and Asterless/Cep152. Here we show that mutant alleles encoding overlapping N- and C-terminal parts of Ana1 are capable of intragenic complementation to rescue radial expansion.
View Article and Find Full Text PDFSci Adv
November 2024
Armenise-Harvard Laboratory of Cell Division, Department of Cellular, Computational and Integrative Biology-CIBIO, University of Trento, Trento, Italy.
Centrosomes are membrane-less organelles that orchestrate a wide array of biological functions by acting as microtubule organizing centers. Here, we report that caspase-2-driven apoptosis is elicited in blood cells failing cytokinesis and that extra centrosomes are necessary to trigger this cell death. Activation of caspase-2 depends on the PIDDosome multi-protein complex, and priming of PIDD1 at extra centrosomes is necessary for pathway activation.
View Article and Find Full Text PDFbioRxiv
October 2024
Department of Pharmacology, University of Washington, Seattle, WA 98195.
Copy number variation (CNV) in the 16p11.2 (BP4-BP5) genomic locus is strongly associated with autism. Carriers of 16p11.
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