Category Ranking
98%
Total Visits
921
Avg Visit Duration
2 minutes
Citations
20
Article Abstract
Background: Nucleophosmin 1 (NPM1) protein is a multifunctional nucleolar chaperone and its gene is the most frequently mutated in Acute Myeloid Leukemia (AML). AML mutations cause the unfolding of the C-terminal domain (CTD) and the protein delocalizing in the cytosol (NPM1c+). Marked aggregation endowed with an amyloid character was assessed as consequences of mutations.
Scope: Herein we analyzed the effects of type C mutation on two protein regions: i) a N-terminal extended version of the CTD, named Cterm_mutC and ii) a shorter polypeptide including the sequences of the second and third helices of the CTD, named H2_mutC.
Major Conclusions: Both demonstrated able to self-assembly with different kinetics and conformational intermediates and to provide fibers presenting large flexible regions.
General Significance: The present study adds a new piece of knowledge to the effects of AML-mutations on structural biology of Nucleophosmin 1, that could be exploited in therapeutic interventions targeting selectively NPMc+.
Download full-text PDF |
Source |
|---|---|
| http://dx.doi.org/10.1016/j.bbagen.2022.130173 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Stabilizing the retromer complex rescues synaptic dysfunction and endosomal trafficking deficits in an Alzheimer's disease mouse model.
Acta Neuropathol Commun
September 2025
Department of Biomedical and Clinical Sciences and Department of Clinical Pathology, Linköping University, 58185, Linköping, Sweden.
Disruptions in synaptic transmission and plasticity are early hallmarks of Alzheimer's disease (AD). Endosomal trafficking, mediated by the retromer complex, is essential for intracellular protein sorting, including the regulation of amyloid precursor protein (APP) processing. The VPS35 subunit, a key cargo-recognition component of the retromer, has been implicated in neurodegenerative diseases, with mutations such as L625P linked to early-onset AD.
View Article and Find Full Text PDFOn the origin of the late-flowering ppd-H1 allele in barley.
Theor Appl Genet
September 2025
Leibniz Institute of Plant Genetics and Crop Research (IPK), 06466, Gatersleben, Germany.
To breed for climate resilient crops, an understanding of the genetic and environmental factors influencing adaptation is critical. Barley provides a model species to study adaptation to climate change. Here we present a detailed analysis of genetic variation at a major photoperiod response locus and relate this to the domestication history and dispersal of barley.
View Article and Find Full Text PDFLoss-of-function mutations in PLD4 lead to systemic lupus erythematosus.
Nature
September 2025
Liangzhu Laboratory, Zhejiang University, Hangzhou, China.
Monogenic lupus offers valuable insights into the underlying mechanisms and therapeutic approaches for systemic lupus erythematosus (SLE). Here we report on five patients with SLE carrying recessive mutations in phospholipase D family member 4 (PLD4). Deleterious variants in PLD4 resulted in impaired single-stranded nucleic acid exonuclease activity in in vitro and ex vivo assays.
View Article and Find Full Text PDFMixed functional consequences of the N651D variant: a case of early-onset developmental and epileptic encephalopathy with parkinsonism.
J Med Genet
September 2025
Department of Pediatrics, Danish Epilepsy Center, Dianalund, Denmark
Rare variants in , the gene encoding the GluA3 subunit of amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA)-type glutamate receptors (AMPARs), are associated with defects in early brain development. Disease-causing variants are generally categorised as either loss of function (LoF) or gain of function (GoF) that appear to be linked to different symptoms. Here, we reported a de novo variant (N651D) that has mixed LoF and GoF in a female patient with a devastating developmental and epileptic encephalopathy, parkinsonism and cortical malformation.
View Article and Find Full Text PDFAllele-specific HLA LOH in solid tumors: distinct patterns by tumor type and potential prognostic relevance.
J Immunother Cancer
September 2025
Affini-T Therapeutics Inc, Watertown, Massachusetts, USA.
T-cell receptors (TCRs) recognize antigens derived from fragments of somatically expressed proteins that are degraded by the proteasome and presented by specific human leukocyte antigen (HLA) molecules. Recent therapeutic advances using the TCR as a tumor-targeting moiety have focused attention on loss of heterozygosity (LOH) as a potential resistance mechanism. Allele-specific LOH, rather than allele-agnostic, is particularly pertinent, but rarely evaluated.
View Article and Find Full Text PDF