Conformational consequences of NPM1 rare mutations: An aggregation perspective in Acute Myeloid Leukemia

Manna, Sara La; Florio, Daniele; Natale, Concetta Di; Napolitano, Fabiana; Malfitano, Anna Maria; Netti, Paolo Antonio; Benedictis, Ilaria De; Marasco, Daniela

doi:10.1016/j.bioorg.2021.104997

Cited by 9 publications

(9 citation statements)

References 45 publications

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“…First of all, the scale bar of the image was measured by using the scale option after using the zoom option from the toolbar. SEM images (1024 × 768 pixels) were obtained, as already described ( Di Natale et al, 2019 ; Bagheri et al, 2021 ; Di Natale et al, 2021a ; Di Natale et al, 2021b ; Di Natale et al, 2021c ; Di Natale et al, 2021d ; Florio et al, 2021 ; Di Natale et al, 2020a ; Di Natale et al, 2020b ; La Manna et al, 2021a ; La Manna et al, 2021b ), and then segmented using the algorithms provided by “DiameterJ Segment” to convert the image into binary forms. Then, segmented images were processed by DiameterJ to measure the diameter of the cellulose bundles and fibers.…”

Section: Methodsmentioning

confidence: 99%

“…All samples were stored at 4°C, and SNE adsorption on cellulose layers was evaluated by confocal microscopy. Samples were imaged using a Leica TCS SP5 STED-CW gated microscope (Leica-Microsystems, Mannheim, Germany) with HCX IRAPO L 25.0 × 0.95 water objective ( Di Natale et al, 2020a ; Jamaledin et al, 2020 ; Di Natale et al, 2021a ; Battisti et al, 2019 ; La Manna et al, 2021a ). A laser source of 488 nm was used to excite the Co-Q10 in the oil core.…”

Section: Methodsmentioning

confidence: 99%

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Engineered Bacterial Cellulose Nanostructured Matrix for Incubation and Release of Drug-Loaded Oil in Water Nanoemulsion

Natale

Gregorio

Lagreca

et al. 2022

Front. Bioeng. Biotechnol.

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Bacterial cellulose (BC) is a highly pure form of cellulose produced by bacteria, which possesses numerous advantages such as good mechanical properties, high chemical flexibility, and the ability to assemble in nanostructures. Thanks to these features, it achieved a key role in the biomedical field and in drug delivery applications. BC showed its ability to modulate the release of several drugs and biomolecules to the skin, thus improving their clinical outcomes. This work displays the loading of a 3D BC nanonetwork with an innovative drug delivery nanoemulsion system. BC was optimized by static culture of SCOBY (symbiotic colony of bacteria and yeast) and characterized by morphological and ultrastructural analyses, which indicate a cellulose fiber diameter range of 30–50 nm. BC layers were then incubated at different time points with a nanocarrier based on a secondary nanoemulsion (SNE) previously loaded with a well-known antioxidant and anti-inflammatory agent, namely, coenzyme-Q10 (Co-Q10). Incubation of Co-Q10–SNE in the BC nanonetwork and its release were analyzed by fluorescence spectroscopy.

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Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Engineered Bacterial Cellulose Nanostructured Matrix for Incubation and Release of Drug-Loaded Oil in Water Nanoemulsion

Natale

Gregorio

Lagreca

et al. 2022

Front. Bioeng. Biotechnol.

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Section: Introductionmentioning

confidence: 99%

“…36,37 Many SAR investigations focused on the conformational consequences of AML mutations provided experimental evidences that protein regions including different mutations are able to self-aggregate in an amyloid way often producing cytotoxic fibers. [38][39][40][41][42][43][44][45][46][47][48][49][50][51] Herein, to obtain hydrogels driven from different interactions we further modified the original hexapeptide by focusing on a five-residues fragment 269-273 (INYVK), deleting the N-terminal Phe residue. We investigated the extremity charge effects on the self-recognition mechanism of four different sequences with N-and C-termini free, or both acetylated/ amidated or alternated (Table 1).…”

Section: Introductionmentioning

confidence: 99%

Hydrogelation tunability of bioinspired short peptides

et al. 2022

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“…The intra [ 45 ] and inter [ 40 ] domain interactions deeply modulate the thermodynamic stability of the entire protein, its nucleolar retention and RNA-binding properties. Our recent studies highlighted an unexpected propensity for amyloid aggregation of several regions of NPMc+ CTD, often providing cytotoxic species [ 46 , 47 , 48 , 49 , 50 , 51 , 52 , 53 , 54 , 55 , 56 , 57 ]. On the basis of the mutual influence of protein domains already observed for NPM1 [ 40 , 45 ], in this study, we investigate the existence of hot spots of aggregation in the entire protein, including NTD and IDR.…”

Section: Introductionmentioning

confidence: 99%

Insights into Network of Hot Spots of Aggregation in Nucleophosmin 1

Florio

Manna

Natale

et al. 2022

IJMS

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In a protein, point mutations associated with diseases can alter the native structure and provide loss or alteration of functional levels, and an internal structural network defines the connectivity among domains, as well as aggregate/soluble states’ equilibria. Nucleophosmin (NPM)1 is an abundant nucleolar protein, which becomes mutated in acute myeloid leukemia (AML) patients. NPM1-dependent leukemogenesis, which leads to its aggregation in the cytoplasm (NPMc+), is still obscure, but the investigations have outlined a direct link between AML mutations and amyloid aggregation. Protein aggregation can be due to the cooperation among several hot spots located within the aggregation-prone regions (APR), often predictable with bioinformatic tools. In the present study, we investigated potential APRs in the entire NPM1 not yet investigated. On the basis of bioinformatic predictions and experimental structures, we designed several protein fragments and analyzed them through typical aggrsegation experiments, such as Thioflavin T (ThT), fluorescence and scanning electron microscopy (SEM) experiments, carried out at different times; in addition, their biocompatibility in SHSY5 cells was also evaluated. The presented data clearly demonstrate the existence of hot spots of aggregation located in different regions, mostly in the N-terminal domain (NTD) of the entire NPM1 protein, and provide a more comprehensive view of the molecular details potentially at the basis of NPMc+-dependent AML.

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Conformational consequences of NPM1 rare mutations: An aggregation perspective in Acute Myeloid Leukemia

Cited by 9 publications

References 45 publications

Engineered Bacterial Cellulose Nanostructured Matrix for Incubation and Release of Drug-Loaded Oil in Water Nanoemulsion

Engineered Bacterial Cellulose Nanostructured Matrix for Incubation and Release of Drug-Loaded Oil in Water Nanoemulsion

Hydrogelation tunability of bioinspired short peptides

Insights into Network of Hot Spots of Aggregation in Nucleophosmin 1

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