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Mouse Anti-FBXW7 (AA 1-354) Recombinant Antibody (CBXF-3570) (CBMAB-F2076-CQ)


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Summary

Host Animal
Mouse
Specificity
Human
Clone
CBXF-3570
Antibody Isotype
IgG1
Application
WB

Basic Information

Specificity
Human
Antibody Isotype
IgG1
Clonality
Monoclonal
Application Notes
The COA includes recommended starting dilutions, optimal dilutions should be determined by the end user.

Formulations & Storage [For reference only, actual COA shall prevail!]

Format
Liquid
Buffer
PBS, pH 7.3, 1% BSA, 50% glycerol
Preservative
0.02% sodium azide
Concentration
1 mg/mL
Storage
Store at +4°C short term (1-2 weeks). Aliquot and store at -20°C long term. Avoid repeated freeze/thaw cycles.
Epitope
AA 1-354

Target

Full Name
F-box and WD repeat domain containing 7
Introduction
This gene encodes a member of the F-box protein family which is characterized by an approximately 40 amino acid motif, the F-box. The F-box proteins constitute one of the four subunits of ubiquitin protein ligase complex called SCFs (SKP1-cullin-F-box), which function in phosphorylation-dependent ubiquitination. The F-box proteins are divided into 3 classes: Fbws containing WD-40 domains, Fbls containing leucine-rich repeats, and Fbxs containing either different protein-protein interaction modules or no recognizable motifs. The protein encoded by this gene was previously referred to as FBX30, and belongs to the Fbws class; in addition to an F-box, this protein contains 7 tandem WD40 repeats. This protein binds directly to cyclin E and probably targets cyclin E for ubiquitin-mediated degradation. Mutations in this gene are detected in ovarian and breast cancer cell lines, implicating the gene's potential role in the pathogenesis of human cancers. Multiple transcript variants encoding different isoforms have been found for this gene.
Entrez Gene ID
55294
UniProt ID
Q969H0
Alternative Names
F-Box And WD Repeat Domain Containing 7; F-Box And WD Repeat Domain Containing 7, E3 Ubiquitin Protein Ligase; F-Box And WD-40 Domain Protein 7 (Archipelago Homolog, Drosophila); F-Box Protein FBX30; SEL-10; Fbx30; SEL10; HCdc4; FBW7; HAgo; F-Box And WD-40 Domain-Containing Protein 7; F-Box/WD Repeat-Containing Protein 7;
Research Area
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 (PubMed:22748924, PubMed:17434132, PubMed:26976582, PubMed:28727686).

Recognizes and binds phosphorylated sites/phosphodegrons within target proteins and thereafter bring them to the SCF complex for ubiquitination (PubMed:22748924, PubMed:26774286, PubMed:17434132, PubMed:26976582, PubMed:28727686).

Identified substrates include cyclin-E (CCNE1 or CCNE2), DISC1, JUN, MYC, NOTCH1 released notch intracellular domain (NICD), NFE2L1, NOTCH2, MCL1, and probably PSEN1 (PubMed:11565034, PubMed:12354302, PubMed:11585921, PubMed:15103331, PubMed:14739463, PubMed:17558397, PubMed:17873522, PubMed:22608923, PubMed:22748924, PubMed:29149593, PubMed:25775507, PubMed:28007894, PubMed:26976582, PubMed:28727686).

Acts as a negative regulator of JNK signaling by binding to phosphorylated JUN and promoting its ubiquitination and subsequent degradation (PubMed:14739463).

Involved in bone homeostasis and negative regulation of osteoclast differentiation (PubMed:29149593).

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 (PubMed:27238018).

Also able to promote 'Lys-63'-linked ubiquitination in response to DNA damage (PubMed:26774286).

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 (PubMed:26774286).
Biological Process
Cellular response to DNA damage stimulus Source: UniProtKB
Cellular response to UV Source: UniProtKB
Lipid homeostasis Source: BHF-UCL
Lung development Source: Ensembl
Negative regulation of gene expression Source: BHF-UCL
Negative regulation of hepatocyte proliferation Source: BHF-UCL
Negative regulation of Notch signaling pathway Source: BHF-UCL
Negative regulation of osteoclast development Source: UniProtKB
Negative regulation of RNA polymerase II regulatory region sequence-specific DNA binding Source: Ensembl
Negative regulation of SREBP signaling pathway Source: BHF-UCL
Negative regulation of triglyceride biosynthetic process Source: BHF-UCL
Notch signaling pathway Source: Ensembl
Positive regulation of epidermal growth factor-activated receptor activity Source: BHF-UCL
Positive regulation of ERK1 and ERK2 cascade Source: BHF-UCL
Positive regulation of oxidative stress-induced neuron intrinsic apoptotic signaling pathway Source: ParkinsonsUK-UCL
Positive regulation of proteasomal protein catabolic process Source: ParkinsonsUK-UCL
Positive regulation of protein targeting to mitochondrion Source: ParkinsonsUK-UCL
Positive regulation of protein ubiquitination Source: ParkinsonsUK-UCL
Positive regulation of ubiquitin-dependent protein catabolic process Source: BHF-UCL
Positive regulation of ubiquitin-protein transferase activity Source: ParkinsonsUK-UCL
Proteasome-mediated ubiquitin-dependent protein catabolic process Source: ARUK-UCL
Protein destabilization Source: Ensembl
Protein stabilization Source: BHF-UCL
Protein ubiquitination Source: UniProtKB
Regulation of autophagy of mitochondrion Source: ParkinsonsUK-UCL
Regulation of cell cycle G1/S phase transition Source: ParkinsonsUK-UCL
Regulation of cell migration involved in sprouting angiogenesis Source: Ensembl
Regulation of circadian rhythm Source: UniProtKB
Regulation of lipid storage Source: BHF-UCL
Regulation of protein localization Source: BHF-UCL
Rhythmic process Source: UniProtKB-KW
SCF-dependent proteasomal ubiquitin-dependent protein catabolic process Source: UniProtKB
Sister chromatid cohesion Source: BHF-UCL
Ubiquitin recycling Source: GO_Central
Vasculature development Source: BHF-UCL
Vasculogenesis Source: Ensembl
Cellular Location
Isoform 1: Nucleoplasm; Chromosome. Localizes to site of double-strand breaks following phosphorylation by ATM.
Isoform 2: Cytoplasm
Isoform 3: Nucleolus
PTM
Phosphorylation at Thr-205 promotes interaction with PIN1, leading to disrupt FBXW7 dimerization and promoting FBXW7 autoubiquitination and degradation (PubMed:22608923). Phosphorylated by ATM at Ser-26 in response to DNA damage, promoting recruitment to DNA damage sites and 'Lys-63'-linked ubiquitination of phosphorylated XRCC4 (PubMed:26774286).
Ubiquitinated: autoubiquitinates following phosphorylation at Thr-205 and subsequent interaction with PIN1. Ubiquitination leads to its proteasomal degradation (PubMed:22608923).
More Infomation

Xia, H., Scholtes, C., Dufour, C. R., Ouellet, C., Ghahremani, M., & Giguère, V. (2022). Insulin action and resistance are dependent on a GSK3β-FBXW7-ERRα transcriptional axis. Nature communications, 13(1), 1-19.

Sanchez‐Burgos, L., Navarro‐González, B., García‐Martín, S., Sirozh, O., Mota‐Pino, J., Fueyo‐Marcos, E., ... & Fernandez‐Capetillo, O. (2022). Activation of the integrated stress response is a vulnerability for multidrug‐resistant FBXW7‐deficient cells. EMBO molecular medicine, 14(9), e15855.

Singh, S., Kumar, S., Srivastava, R. K., Nandi, A., Thacker, G., Murali, H., ... & Chakrabarti, R. (2020). Loss of ELF5–FBXW7 stabilizes IFNGR1 to promote the growth and metastasis of triple-negative breast cancer through interferon-γ signalling. Nature cell biology, 22(5), 591-602.

Cui, D., Xiong, X., Shu, J., Dai, X., Sun, Y., & Zhao, Y. (2020). FBXW7 confers radiation survival by targeting p53 for degradation. Cell Reports, 30(2), 497-509.

Yumimoto, K., & Nakayama, K. I. (2020, December). Recent insight into the role of FBXW7 as a tumor suppressor. In Seminars in cancer biology (Vol. 67, pp. 1-15). Academic Press.

Xu, Y., Qiu, A., Peng, F., Tan, X., Wang, J., & Gong, X. (2020). Exosomal transfer of circular RNA FBXW7 ameliorates the chemoresistance to oxaliplatin in colorectal cancer by sponging miR-18b-5p. Neoplasma.

Sailo, B. L., Banik, K., Girisa, S., Bordoloi, D., Fan, L., Halim, C. E., ... & Kunnumakkara, A. B. (2019). FBXW7 in cancer: what has been unraveled thus far?. Cancers, 11(2), 246.

Lan, H., Tan, M., Zhang, Q., Yang, F., Wang, S., Li, H., ... & Sun, Y. (2019). LSD1 destabilizes FBXW7 and abrogates FBXW7 functions independent of its demethylase activity. Proceedings of the National Academy of Sciences, 116(25), 12311-12320.

Zhang, G., Zhu, Q., Fu, G., Hou, J., Hu, X., Cao, J., ... & Cui, H. (2019). TRIP13 promotes the cell proliferation, migration and invasion of glioblastoma through the FBXW7/c-MYC axis. British journal of cancer, 121(12), 1069-1078.

Yeh, C. H., Bellon, M., & Nicot, C. (2018). FBXW7: a critical tumor suppressor of human cancers. Molecular cancer, 17(1), 1-19.

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For research use only. Not intended for any clinical use.

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