Recombinant Human NPM1 & ALK (F1174L) Protein

Name: Recombinant Human NPM1 & ALK (F1174L) Protein
Brand: Beta LifeScience
SKU: BL-0252SG
Availability: InStock

Collections: Other recombinant proteins, Recombinant proteins

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Product Overview

Tag	GST
Host Species	Human
Accession	U04946
Synonym	NPM1: B23; NPMALK: ALK (Ki-1), CD246, NBLST3, TFG/ALK
Background	NPM1-ALK which belongs to the insulin receptor superfamily which comprises an extracellular domain, a hydrophobic stretch corresponding to a single pass transmembrane region, and an intracellular kinase domain. CD246 plays an important role in the development of the brain and exerts its effects on specific neurons in the nervous system. ALK-positive neoplasms represent a distinct entity because the morphology of the tumors is often neither anaplastic nor large cell and the tumors should be referred to as ALK lymphomas (1). CD246 has been found to be rearranged, mutated, or amplified in a series of tumours including anaplastic large cell lymphomas, neuroblastoma, and non-small cell lung cancer. STAT5A is epigenetically silenced by the tyrosine kinase NPM1-ALK and acts as a tumor suppressor by reciprocally inhibiting NPM1-ALK expression (2).
Description	Recombinant human fusion protein NPM1 (1-117)-ALK (F1174L) (1058-end) was produced by baculovirus in Sf9 insect cells, fused with a GST tag at N-terminus. This protein is purified with our unique purification methods.
Source	Sf9 insect cells
AA Sequence	1058a.a.-end
Molecular Weight	~108 kDa
Purity	For specific purity information on a given lot, see related COA.
Endotoxin	< 1.0 EU per μg of the protein as determined by the LAL method
Bioactivity	Active
Formulation	Recombinant protein is supplied in 50mM Tris-HCl, pH 7.5, 50mM NaCl, 10mM Glutathione, 0.25mM DTT, 0.1mM EDTA, 0.1mM PMSF and 25% glycerol.
Stability	The recombinant protein is stable for up to 12 months at -70°C
Usage	For Research Use Only
Storage	Recombinant Human NPM1 & ALK (F1174L) Protein should be stored should be stored at < -70°C. It is recommended that the protein be aliquoted for optimal storage. Avoid repeated freeze-thaw cycles.

Target Details

Target Function	Involved in diverse cellular processes such as ribosome biogenesis, centrosome duplication, protein chaperoning, histone assembly, cell proliferation, and regulation of tumor suppressors p53/TP53 and ARF. Binds ribosome presumably to drive ribosome nuclear export. Associated with nucleolar ribonucleoprotein structures and bind single-stranded nucleic acids. Acts as a chaperonin for the core histones H3, H2B and H4. Stimulates APEX1 endonuclease activity on apurinic/apyrimidinic (AP) double-stranded DNA but inhibits APEX1 endonuclease activity on AP single-stranded RNA. May exert a control of APEX1 endonuclease activity within nucleoli devoted to repair AP on rDNA and the removal of oxidized rRNA molecules. In concert with BRCA2, regulates centrosome duplication. Regulates centriole duplication: phosphorylation by PLK2 is able to trigger centriole replication. Negatively regulates the activation of EIF2AK2/PKR and suppresses apoptosis through inhibition of EIF2AK2/PKR autophosphorylation. Antagonizes the inhibitory effect of ATF5 on cell proliferation and relieves ATF5-induced G2/M blockade. In complex with MYC enhances the transcription of MYC target genes.
Subcellular Location	Nucleus, nucleolus. Nucleus, nucleoplasm. Cytoplasm, cytoskeleton, microtubule organizing center, centrosome. Note=Generally nucleolar, but is translocated to the nucleoplasm in case of serum starvation or treatment with anticancer drugs. Has been found in the cytoplasm in patients with primary acute myelogenous leukemia (AML), but not with secondary AML. Can shuttle between cytoplasm and nucleus. Co- localizes with the methylated form of RPS10 in the granular component (GC) region of the nucleolus. Colocalized with nucleolin and APEX1 in nucleoli. Isoform 1 of NEK2 is required for its localization to the centrosome during mitosis.
Protein Families	Nucleoplasmin family
Database References	HGNC: 7910 OMIM: 164040 KEGG: hsa:4869 STRING: 9606.ENSP00000296930 UniGene: Hs.557550
Associated Diseases	A chromosomal aberration involving NPM1 is found in a form of non-Hodgkin lymphoma. Translocation t(2;5)(p23;q35) with ALK. The resulting chimeric NPM1-ALK protein homodimerize and the kinase becomes constitutively activated.

Gene Functions References

NPM1 and SURF6 form heterotypic liquid-like droplets in the nucleolus. PMID: 29483575
High NPM1 expression is associated with tongue neoplasms. PMID: 29746960
his meta-analysis indicated that NPM may act as a valuable prognosis biomarker and a potential therapeutic target in human solid tumors. PMID: 30126359
this paper shows that viral nucleocapsid interacts with NPM1 and protects it from proteolytic cleavage, enhancing Cell survival, and is involved in porcine epidemic diarrhea virus growth PMID: 28045037
DNMT3A R882 mutation plays an important role in CN-AML patients' prognosis and clinical outcomes in the presence and absence of NPM1 and FLT3 mutations. PMID: 29079128
Mutation in NPM1 gene is associated with Acute Myeloid Leukemia. PMID: 29530994
Nucleoplasmic translocation of NPM1 is a prerequisite for stress-induced activation of p53. PMID: 27886181
NPM1 gene B type mutation enhanced the proliferation and invasion of THP-1 AML cells through the regulation of TIMP-2, MMP-2, Ang-1, c-myc and CCND1 PMID: 29441887
In this study, FLT3 and NPM1 mutations were evaluated in adult Iranian patients with de novo cytogenetically normal acute myeloid leukemia and its correlations with clinical and laboratory parameters were also assessed. PMID: 28294102
These observations demonstrated that the expression and localization of NPM affected the homeostatic balance of oxidative stress in tumor cells via PRDX6 protein. The regulation axis of NPM/PRDX/ROS may provide a novel therapeutic target for cancer treatment. PMID: 28513872
ese results enhance our understanding of the molecular mechanisms that govern nucleoli formation by demonstrating that PPM1D regulates nucleolar formation by regulating NPM phosphorylation status through a novel signalling pathway, PPM1D-CDC25C-CDK1-PLK1 PMID: 27619510
Data suggest that the direct interaction of several regions of nucleophosmin 1 (NPM1) C-terminal domain (CTD) with cellular membranes could be implicated in diseases where NPM1 is mutated and/or where its overexpression is cytoxic. PMID: 29330024
Mechanically, mutant NPM1 interacted with PML and mediated its delocalization as well as stabilization contributing to elevated autophagic activity and leukemic cell survival in vitro. PMID: 28740552
Mutation analysis in NPM1 in acute myeloid leukemia. PMID: 27071442
We conclude that the degradation of NPM1 and HEXIM1 through autophagy in certain AML subsets contributes to the activation of the BET pathway in these cells. PMID: 27732946
miR-10b exerts its effects by repressing the translation of KLF4 and that NPM1-mA inhibits myeloid differentiation through the miR-10b/KLF4 axis. PMID: 27669739
NPM1 may play an important role in tumor progress in salivary gland adenoid cystic carcinoma (SACC) and is a potential biomarker for SACC. PMID: 27501253
Data show that phosphorylated forms of nucleophosmin 1 (NPM1) interact with androgen receptor (AR) in nucleoplasm. PMID: 26993766
Studies indicate that nucleophosmin 1 (NPM1) has been considered as a promising target for the treatment of both haematologic and solid malignancies. PMID: 27058426
Work identifies the TP53 tumor suppressor as a novel target through which NPM1-RARA impacts leukemogenesis. PMID: 26754533
These results suggested that relocation of NPM altered its interactional network and consequently disturbed the primary functions, including cell proliferation, adhesion, migration, and invasion. NPM plays a promotional role in cancer. PMID: 28262969
the consequence of mutations in NPM1 and possible mechanisms through which mutations lead to leukemogenesis (review0. PMID: 28111462
NPM1 mutation but not RUNX1 mutation or multilineage dysplasia defines a prognostic subgroup within de novo acute myeloid leukemia lacking recurrent cytogenetic abnormalities PMID: 28370403
Nucleophosmin 1 (NPM1) mutations in chronic myelomonocytic leukemia and their prognostic relevance. PMID: 28707414
Multivariable analyses on time to relapse and OS revealed pre-transplant NPM1 MRD levels >1% as an independent prognostic factor for poor survival after allogeneic HSCT, whereas FLT3-ITD had no impact. Notably, outcome of patients with pre-transplant NPM1 MRD positivity >1% was as poor as that of patients transplanted with RD. PMID: 27471865
Our results indicate that CD4 expression and older age are adverse prognostic factors in wild-type NPM1, FLT3-ITD-negative CN-AML. PMID: 28318150
NPM1-dependent nucleolar PIDDosome is a key initiator of the caspase-2 activation cascade. PMID: 28432080
Data indicate that NPM-ALK was distributed in equal amounts between the cytoplasm and the nucleus. PMID: 26657151
The aim of this review is to look at the less well-described role of NPM1 in the DNA repair pathways as well as the role of NPM1 in the regulation of apoptosis and its mutation in cancers. [review] PMID: 27553022
revealed that the localization of fluorescently labeled NPM is affected by the interaction between various forms of the protein PMID: 28384310
value of mutated NPM1 in AML in risk assessment and evaluating prognosis PMID: 27416910
NPM1 downregulation by P-STAT5 is mediated by impairing the BRCA1-BARD1 ubiquitin ligase, which controls the stability of NPM1. In turn, decreased NPM1 levels led to suppression of p53 expression, resulting in enhanced cell survival. PMID: 28005077
These results suggest that the p38/NPM/PP2A complex acts as a dynamic sensor, allowing endothelial cells to react rapidly to acute oxidative stress. PMID: 27142525
Nucleophosmin-anaplastic lymphoma kinase serves as the founding member of the ALK fusion protein family, and its role in malignant cell transformation is by far the best characterized and, thus, is the main focus of this review. [review] PMID: 27879258
data suggest that NPM1 mutations are a secondary or late event in the pathogenesis of AML and are preceded by founder mutations in genes that may be associated with recently described preclinical states such as clonal hematopoiesis of indeterminate potential or clonal cytopenias of undetermined significance. PMID: 28152414
Mutations of NPM1 gene is associated with Acute myeloid leukemia. PMID: 27636548
RQ-PCR of the NPM1 type A mutation was more sensitive and reliable than MFC for determination of minimal residual disease , which might have clinical implications. PMID: 27191933
The results demonstrated that NPM downregulation markedly reversed the effects of multidrug resistance in in human hepatoma cells. In addition, NPM downregulation reduced P-glycoprotein expression, as well as MDR1 expression. PMID: 28259962
Only karyotype and mutated NPM1 (NPM1mut) were independent predictors of survival in acute myeloid leukemia PMID: 27643573
Our study provides a method for systematic characterization of NPM1 oligomer formation changes and for screening inhibitors of NPM1 oligomerization. PMID: 27983985
Mutation of NPM1 determined by the widely available and inexpensive Immunohistochemical(IHC )agrees closely with results of the standard molecular methods. Thus, technically and financially not well endowed laboratories can provide the prognostically and potentially therapeutically important information on NPM1 mutation using IHC. PMID: 27748301
In pediatric patients with AML from Argentina, a favorable prognosis of AML with genotype NPM1-mutated/FLT3-ITD-negative was confirmed. PMID: 27436336
This study investigated the expression level of miR-1, miR-486, and let-7a in 45 CN-AML patients well characterized for FLT3 and/or NPM1 mutations using real-time quantitative RT-PCR and evaluated the association between candidate miRs expression and clinical features PMID: 26526573
data showed that the pre-transplant level of MRD in patients with normal karyotype AML harboring NPM1 mutation in CR provides important prognostic information, which as an independent prognostic factor predicts transplant results PMID: 27798920
Molecular subtypes of NPM1 mutations have different clinical profiles, specific patterns of accompanying molecular mutations and varying outcomes in intermediate risk acute myeloid leukemia. PMID: 26471486
In this study, a direct association was observed between NPMc(+)expression in AML, reduced antioxidant responses, and enhanced sensitivity to an oral proteasome inhibitor that induces oxidative stress. PMID: 26634271
analysis of the frequency and features of Acute myeloid leukemia with mutated NPM1 in Indian patients PMID: 26669619
Nucleophosmin Interacts with promyelocytic leukemia protein/retinoic acid receptor alpha Only in the Resistant Cell Line. PMID: 26997274
Longitudinal qPCR monitoring of nucleophosmin 1 mutations after allogeneic hematopoietic stem cell transplantation to predict AML relapse. PMID: 26642331
results suggest that cup-like nuclei represent an important morphologic clue that can predict NPMc+ AML and guide toward prioritizing the further workup of AML patients PMID: 26200838

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