Name: Recombinant Human F-box/WD repeat-containing protein 7 (FBXW7)
Brand: CUSABIO
SKU: CSB-CF822163HU

Product Details

Purity

Greater than 90% as determined by SDS-PAGE.

Target Names

FBXW7

Uniprot No.

Q969H0

Research Area

Cell Biology

Alternative Names

FBXW7; FBW7; FBX30; SEL10; F-box/WD repeat-containing protein 7; Archipelago homolog; hAgo; F-box and WD-40 domain-containing protein 7; F-box protein FBX30; SEL-10; hCdc4

Species

Homo sapiens(Human)

Source

in vitro E.coli expression system

Expression Region

1-707aa

Target Protein Sequence

MNQELLSVGSKRRRTGGSLRGNPSSSQVDEEQMNRVVEEEQQQQLRQQEEEHTARNGEVVGVEPRPGGQNDSQQGQLEENNNRFISVDEDSSGNQEEQEEDEEHAGEQDEEDEEEEEMDQESDDFDQSDDSSREDEHTHTNSVTNSSSIVDLPVHQLSSPFYTKTTKMKRKLDHGSEVRSFSLGKKPCKVSEYTSTTGLVPCSATPTTFGDLRAANGQGQQRRRITSVQPPTGLQEWLKMFQSWSGPEKLLALDELIDSCEPTQVKHMMQVIEPQFQRDFISLLPKELALYVLSFLEPKDLLQAAQTCRYWRILAEDNLLWREKCKEEGIDEPLHIKRRKVIKPGFIHSPWKSAYIRQHRIDTNWRRGELKSPKVLKGHDDHVITCLQFCGNRIVSGSDDNTLKVWSAVTGKCLRTLVGHTGGVWSSQMRDNIIISGSTDRTLKVWNAETGECIHTLYGHTSTVRCMHLHEKRVVSGSRDATLRVWDIETGQCLHVLMGHVAAVRCVQYDGRRVVSGAYDFMVKVWDPETETCLHTLQGHTNRVYSLQFDGIHVVSGSLDTSIRVWDVETGNCIHTLTGHQSLTSGMELKDNILVSGNADSTVKIWDIKTGQCLQTLQGPNKHQSAVTCLQFNKNFVITSSDDGTVKLWDLKTGEFIRNLVTLESGGSGGVVWRIRASNTKLVCAVGSRNGTEETKLLVLDFDVDMK
Note: The complete sequence including tag sequence, target protein sequence and linker sequence could be provided upon request.

Mol. Weight

83.7kDa

Protein Length

Full Length

Tag Info

N-terminal 6xHis-tagged

Form

Liquid or Lyophilized powder
Note: We will preferentially ship the format that we have in stock, however, if you have any special requirement for the format, please remark your requirement when placing the order, we will prepare according to your demand.

Buffer

If the delivery form is liquid, the default storage buffer is Tris/PBS-based buffer, 5%-50% glycerol.
Note: If you have any special requirement for the glycerol content, please remark when you place the order.
If the delivery form is lyophilized powder, the buffer before lyophilization is Tris/PBS-based buffer, 6% Trehalose, pH 8.0.

Reconstitution

We recommend that this vial be briefly centrifuged prior to opening to bring the contents to the bottom. Please reconstitute protein in deionized sterile water to a concentration of 0.1-1.0 mg/mL.We recommend to add 5-50% of glycerol (final concentration) and aliquot for long-term storage at -20°C/-80°C. Our default final concentration of glycerol is 50%. Customers could use it as reference.

Troubleshooting and FAQs

Protein FAQs

Storage Condition

Store at -20°C/-80°C upon receipt, aliquoting is necessary for mutiple use. Avoid repeated freeze-thaw cycles.

Shelf Life

The shelf life is related to many factors, storage state, buffer ingredients, storage temperature and the stability of the protein itself.
Generally, the shelf life of liquid form is 6 months at -20°C/-80°C. The shelf life of lyophilized form is 12 months at -20°C/-80°C.

Lead Time

3-7 business days

Notes

Repeated freezing and thawing is not recommended. Store working aliquots at 4°C for up to one week.

Datasheet & COA

Please contact us to get it.

Description

The production of this Recombinant Human FBXW7 protein required the insertion of a DNA fragment (FBXW7, 1-707aa) into an expression vector (a plasmid vector) and the transferral of this vector into in vitro E.coli cells (the step of transformation). The cells were then cultured and induced to express the FBXW7 protein. This recombinant protein was fused with N-terminal 6xHis tag. Its purity is 90%+ determined by SDS-PAGE.

FBXW7 functions as the substrate recognition component of the SCF E3 ubiquitin ligase. It is a key tumor suppressor and one of the most frequently deregulated ubiquitin-proteasome system proteins in human cancer. It specifically controls proteasomal degradation of oncoproteins such as cyclin E, c-Myc, Mcl-1, mTOR, Jun, Notch, and AURKA. FBXW7 gene mutations or decreased expression have a crucial biological function in tumor development. FBXW7 is also involved in embryonic development, as well as the proliferation and maturation of stem cell populations.

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■ Q&A

Can you tell me the protein concentration for your item CSB-CF822163HU?

Thanks for your inquiry. The protein concentration of the last lot is 0.2 mg/ml.

Target Background

Function

Substrate recognition component of a SCF (SKP1-CUL1-F-box protein) E3 ubiquitin-protein ligase complex which mediates the ubiquitination and subsequent proteasomal degradation of target proteins. Recognizes and binds phosphorylated sites/phosphodegrons within target proteins and thereafter bring them to the SCF complex for ubiquitination. Identified substrates include cyclin-E (CCNE1 or CCNE2), DISC1, JUN, MYC, NOTCH1 released notch intracellular domain (NICD), NFE2L1, NOTCH2, MCL1, and probably PSEN1. Acts as a negative regulator of JNK signaling by binding to phosphorylated JUN and promoting its ubiquitination and subsequent degradation. Involved in bone homeostasis and negative regulation of osteoclast differentiation. Regulates the amplitude of the cyclic expression of hepatic core clock genes and genes involved in lipid and glucose metabolism via ubiquitination and proteasomal degradation of their transcriptional repressor NR1D1; CDK1-dependent phosphorylation of NR1D1 is necessary for SCF(FBXW7)-mediated ubiquitination. Also able to promote 'Lys-63'-linked ubiquitination in response to DNA damage. The SCF(FBXW7) complex facilitates double-strand break repair following phosphorylation by ATM: phosphorylation promotes localization to sites of double-strand breaks and 'Lys-63'-linked ubiquitination of phosphorylated XRCC4, enhancing DNA non-homologous end joining.

Gene References into Functions

Multivalent Interactions with Fbw7 and Pin1 Facilitate Recognition of c-Jun by the Fbw7. PMID: 29225075
FBXW7 is critical for RIG-I stabilization during antiviral responses. PMID: 28287082
Expression of miR-223 is negatively correlated with F-box and WD repeat domain-containing 7 (FBXW7) expression in cells and tissues. PMID: 29701752
FBXW7 conduction of tumour suppression was partly through degrading Snai1 directly for ubiquitylating regulation in NSCLC. PMID: 30094882
Data showed that both chemo and radiation sensitivity increased in TE-8 and KYSE140 cells overexpressing FBXW7 compared with mock cells because of the degradation of the anti-apoptotic protein MCL1. PMID: 30098297
Fbw7 mutations shifted cellular metabolism toward oxidative phosphorylation and caused context-specific metabolic vulnerabilities. PMID: 29735700
TINCR suppressed proliferation and invasion through regulating miR-544a/FBXW7 axis in lung cancer. PMID: 29324317
Low FBXW7 expression is associated with non-small cell lung cancer. PMID: 28656290
we identified F-box and WD repeat domain-containing 7 (FBXW7) protein as a direct functional target of miR-25 in esophageal squamous cell carcinoma (ESCC). In conclusion, the present study supports the potential of miR-25 as a prognostic predictor with its high expression in cancer tissues and its association with tumor progression by targeting FBXW7 in ESCC PMID: 29048664
FBXW7 was significantly downregulated in renal cell carcinoma cell lines. Upregulation of FBXW7 in 786-O and ACHN cell lines significantly inhibited cell migration, invasion and EMT. PMID: 29097832
FBXW7 missense mutation is associated with metastatic colorectal adenocarcinoma. PMID: 28424412
miR-92b-3p inhibition prevented colorectal cancer proliferation, invasion, and migration by upregulating FBXW7, which might suggest the potential role of miR-92b-3p in colorectal carcinogenesis and metastasis. PMID: 29638162
FBXW7 is markedly downregulated in the liver of obese subjects. A functional low-frequency human FBXW7 coding variant (p.Ala204Thr) is associated with elevated blood glucose and T2DM risk in a Chinese population. Mechanistically, FBXW7 directly binds to hepatokine fetuin-A to induce its ubiquitination and subsequent proteasomal degradation, comprising an important mechanism maintaining glucose homeostasis. PMID: 29475832
Our findings suggest FBW7 mutational status and Mcl-1 stability as key determinants of response to Hsp90 inhibitors, which provides a rationale for using FBW7 genotype for potential patient stratification, and for drug combinations with Hsp90 inhibitors that can effectively overcome Mcl-1-mediated resistance. PMID: 28619760
a cancer stem cell-specific FBXW7-regulatory mechanism is strongly associated with resistance to chemotherapeutic agents. PMID: 28699179
FBW7 promoted gemcitabine sensitivity via upregulation of equilibrative nucleoside transporter 1 (ENT1) at the protein level rather than the transcriptional level. PMID: 28765935
FBW7 overexpression downregulated Aurora B, Mcl1 and Notch1 levels. PMID: 29427543
FBXW7 was a downstream target of miR-367 and CASC2 prohibited epithelial-to-mesenchymal transition progression and subsequently exerted its anti-metastatic effects via CASC2/miR-367/FBXW7 axis in hepatocellular carcinoma cells. PMID: 28716020
FBW7 cooperated with gamma-catenin to inhibit G2/M cell cycle transition and cell proliferation. PMID: 29408378
We also propose a model for the stabilization mechanism in which binding to Aurora-A alters how N-Myc interacts with SCF(FbxW7) to disfavor the generation of Lys48-linked polyubiquitin chains PMID: 27837025
We find that both primary and recurrent Squamous cell carcinoma of the anal canal (ASCC) tumors harbor mutations in genes, such as PIK3CA and FBXW7, that are also mutated in other HPV-associated cancers. Overall mutational burden was not significantly different in pre- versus post-CRT tumors, and several examples of shared clonal driver mutations were identified PMID: 27852700
We have identified low FBXW7 expression as a potential powerful marker of poor prognosis in patients with gastric adenocarcinoma. Furthermore, in view of the different chemotherapeutics outcomes found in this large database study, FBXW7 may serve as an important predictor in chemotherapeutic responses. PMID: 28464881
Fbxw7 haploinsufficiency increased the risk of gastric carcinogenesis induced by MNU, which is associated with the accumulation of DNA damage as well as c-Myc oncoprotein. PMID: 28422719
EglN2 might act as an FBW7 ubiquitin ligase substrate contributing to the progression of triple negative breast cancer. PMID: 28036276
FAM83D knockdown up-regulated the protein expression level of F-box and WD repeat domain-containing 7 (FBXW7), but diminished the Notch1 protein expression level. PMID: 28407575
Thus, our study uncovers a novel regulatory mechanism underlying which KLF10 stability and its biological function are mediated by FBW7. PMID: 29198712
Results found it showed reduced expression in diffuse large B-cell lymphoma (DLBCL), which was associated with a poor outcome. Fbw7 expression promotes apoptosis in DLBCL cell lines. Furthermore, the study demonstrated that Fbw7 targets Stat3 and especially activated Stat3 for ubiquitylation to regulate its stability. PMID: 28069035
Data suggest that FBXW7, MCL1 and PLK1 may be relevant predictive markers of tumor progression and response to paclitaxel treatment. PMID: 27409838
FBW7 serves as a negative regulator of glucose metabolism through regulation of the c-Myc/TXNIP axis in pancreatic cancer. PMID: 26983463
increased expression of activated NOTCH1 was found in NOTCH1/FBXW7 hotspot exon-mutated cases. Study suggests that NOTCH1/FBXW7 hotspot-mutated T-ALL cases had better response to ALL BFM-95 protocol. PMID: 29200162
Study identify SCF-FBW7 as a ubiquitin E3 ligase that regulates the cellular FAAP20 levels and Fanconi anemia (FA) pathway. Deregulation of the GSK3beta- and FBW7-dependent FAAP20 degradation leads to a defect in the FA pathway, establishing a direct link between FBW7 and DNA repair. PMID: 27232758
HRAS mutations were more common in epithelial-myoepithelial carcinomas (EMCAs) with intact PLAG1 and HMGA2. Most EMCAs arose ex pleomorphic adenoma (PA)and the genetic profile of EMCA varies with the absence or presence of preexisting PA and its cytogenetic signature. Progression to higher grade EMCA with intact PLAG1 and HMGA2 correlates with the presence of TP53, FBXW7 mutations, or SMARCB1 deletion. PMID: 29135520
Data indicate the SCF(Fbxw7)-independent regulatory mechanism centred on the highly conserved lysine-52 (K52) within MYC Box I. PMID: 28806398
Results identified FBXW7 as a functional target of miR-155-3p and demonstrated an involvement of FBXW7 in the effects of increased miR-155-3p on promoting clone formation and proliferation of hepatocellular carcinoma. PMID: 27306418
FBXW7alpha inhibits breast cancer cells survival by promoting GATA3 degradation/destabilizing GATA3. PMID: 28722108
Loss of FBW7 expression is associated with breast cancer. PMID: 28760857
FBXW7 could be a potential biomarker for predicting not only the clinical response to chemoradiotherapy but also overall survival in patients with oral squamous cell carcinoma PMID: 29072128
Our results reveal a new mechanism of ZNF322A oncoprotein destruction regulated by the CK1delta/GSK3beta/FBXW7a axis. Deregulation of this signaling axis results in ZNF322A overexpression and promotes cancer progression PMID: 28581525
Low FBXW7 expression is associated with pancreatic cancer. PMID: 28423622
siRNA interference of FBXW7 reversed the inhibitory effect of MAGEA1 on migration and proliferation of MCF-7 and MDA-MB-231 cells. PMID: 28459460
Endogenous circRNA encodes a functional protein in human cells, and circ-FBXW7 and FBXW7-185aa have potential prognostic implications in brain cancer. PMID: 28903484
Dual FBXW7-GAK inhibition increases multipolar mitoses. PMID: 28829765
EXT1, a gene not previously linked to acute lymphoblastic leukemia via mutations, is a common interactor of NOTCH1 and FBXW7 regulating the NOTCH pathway in an FBXW7-dependend manner. PMID: 27229929
C-MYC and FBXW7 affect Adult T-cell Leukemia/Lymphoma proliferation and progression, and low FBXW7 may increase C-MYC expression. C-MYC was a critical prognostic factor in Adult T-cell Leukemia/Lymphoma patients. PMID: 28498285
The findings reveal a PLK1-Fbw7-Myc signaling circuit that underlies tumorigenesis and validate PLK1 inhibitors, alone or with Bcl2 antagonists, as potential effective therapeutics for MYC-overexpressing cancers. PMID: 27773673
Findings demonstrate that Fbw7 targets CDX2 for ubiquitin-mediated proteasome degradation in a GSK3b-dependent manner where GSK3b presumably phosphorylates CDX2 within the two potential phosphodegron motifs. PMID: 27470268
Plk2 represents an independent prognostic marker and regulates tumor growth and apoptosis by targeting Fbxw7/Cyclin E pathway in colorectal carcinoma. PMID: 27423313
Here, we show that the SCFFBW7alpha ubiquitin ligase targets SOX9 for proteasomal degradation and provide experimental evidence of a role for FBW7 in modulating medulloblastoma malignancy and cisplatin resistance by controlling SOX9 proteolysis. PMID: 27625374
The authors show that STYX binds to the F-box domain of FBXW7 and disables its recruitment into the SCF ubiquitin ligase complex. PMID: 28007894
In colorectal cancers, mutations in the FBXW7 gene were more common in the younger cohort (27.5% vs 9.7%; P = .0022) as were mutations in the proofreading domain of polymerase epsilon catalytic subunit (POLE) (9.8% vs 1%; P = .0048). PMID: 27244218

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Subcellular Location

[Isoform 1]: Nucleus, nucleoplasm. Chromosome.; [Isoform 2]: Cytoplasm.; [Isoform 3]: Nucleus, nucleolus.

Tissue Specificity

[Isoform 1]: Widely expressed.; [Isoform 3]: Expressed in brain.

Database Links

HGNC: 16712

OMIM: 606278

KEGG: hsa:55294

STRING: 9606.ENSP00000281708

UniGene: Hs.561245

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