Recombinant Human NPM1 & ALK (F1174L) Protein
Beta LifeScience SKU/CAT #: BL-0252SG
Recombinant Human NPM1 & ALK (F1174L) Protein
Beta LifeScience SKU/CAT #: BL-0252SG
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|NPM1: B23; NPMALK: ALK (Ki-1), CD246, NBLST3, TFG/ALK
|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).
|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.
|Sf9 insect cells
|For specific purity information on a given lot, see related COA.
|< 1.0 EU per μg of the protein as determined by the LAL method
|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.
|The recombinant protein is stable for up to 12 months at -70°C
|For Research Use Only
|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.
|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.
|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.
|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