New insights into the nucleophosmin/nucleoplasmin family of nuclear chaperones

Abstract

Basic proteins and nucleic acids are assembled into complexes in a reaction that must be facilitated by nuclear chaperones in order to prevent protein aggregation and formation of non-specific nucleoprotein complexes. The nucleophosmin/nucleoplasmin (NPM) family of chaperones [NPM1 (nucleophosmin), NPM2 (nucleoplasmin) and NPM3] have diverse functions in the cell and are ubiquitously represented throughout the animal kingdom. The importance of this family in cellular processes such as chromatin remodeling, genome stability, ribosome biogenesis, DNA duplication and transcriptional regulation has led to the rapid growth of information available on their structure and function. The present review covers different aspects related to the structure, evolution and function of the NPM family. Emphasis is placed on the long-term evolutionary mechanisms leading to the functional diversification of the family members, their role as chaperones (particularly as it pertains to their ability to aid in the reprogramming of chromatin), and the importance of NPM2 as an essential component of the amphibian chromatin remodeling machinery during fertilization and early embryonic development.

Nucleophosmin/B23 Negatively Regulates GCN5-dependent Histone Acetylation and Transactivation

“…B23 Regulates GCN5-mediated Histone Acetylation-Both B23 and GCN5 are involved in histone post-translational regulation (1,17). B23 can bind histones functioning as a histone chaperone and promote nucleosomal assembly in vitro (17), whereas recombinant full-length mammalian GCN5 is competent for the acetylation of nucleosomal histones (27).…”

“…B23 can bind histones functioning as a histone chaperone and promote nucleosomal assembly in vitro (17), whereas recombinant full-length mammalian GCN5 is competent for the acetylation of nucleosomal histones (27). In order to scrutinize the biological and biochemical significance of the The immunoprecipitates were then separated by SDS-PAGE and probed with anti-B23 or GCN5 antibodies.…”

“…B23 is frequently targeted for genetic mutations by chromosomal translocations and point mutations in lymphomas and leukemias and is one of the most frequently mutated genes in acute myeloid leukemia (13). It has also been established that B23 can function as an acidic histone chaperone that helps assemble nucleosomes in vitro (17). B23 can either repress (18,19) or stimulate transcription (20,21), depending on the promoter context and/or inter-acting transcription factors.…”

The leukemia-associated cytoplasmic nucleophosmin mutant is an oncogene with paradoxical functions: Arf inactivation and induction of cellular senescence

“…It has been recently shown that oncogene-induced senescence is associated with signs of DNA replication stress (Di Micco et al, 2006). Considering that wild-type NPM has a function in modulating chromosome condensation/decondensation and is recruited to sites of dsDNA breaks (Frehlick et al, 2007), we hypothesized that NPMc þ may lead to senescence by blocking the NPM function in DNA damage response. However, at the passage where senescence and growth curve was analysed, overexpression of NPMc þ in wildtype MEFs was not accompanied by positivity for markers characteristically induced in cells suffering DNA damage as shown by the scarce nuclear staining NPMc + is an oncogene K Cheng et al of phospho-histone H2A.X (Ser139), unlike those of the UV-irradiated MEFs (Supplementary Figure 3A).…”

Nucleophosmin mutations in acute myeloid leukemia: A tale of protein unfolding and mislocalization

“…They can be further classified into four groups, based on sequence similarities: NPM1 (nucleophosmin), NPM2 (nucleoplasmin), NPM3, and NPM-like invertebrate proteins. 11 The hallmark of all family members is the presence of a well-conserved N-terminal core domain that, following a short methionine-rich unstructured sequence of unknown function, extends for 100 residues ( Fig. 1) and folds as a eight-stranded beta-barrel, composed of two opposing antiparallel fourstranded sheets.…”