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Two FBXW7 mutations (p.R479P and p.L443H), were identified from a study of 145 (1.4%) cervical squamous cell carcinomas. The p.L443H somatic mutation has not been previously reported. Functional assays showed that both of these FBXW7 mutations could promote cell proliferation, migration, and invasion.
FBXW7, a tumor suppressor, inhibits breast cancer cell proliferation and promotes apoptosis at least partially through targeting MTDH for proteolysis
Loss of FBXW7 indirectly modulates RhoB activity via alteration of the cholesterol biosynthesis pathway.
loss of FBXW7 promotes non-small-cell lung cancer progression as well as gefitinib resistance.
the congenital CHEK2 inactivation is strongly associated with the risk of MDS and with a poorer prognosis of the disease. However, the chromosomal instability in AML is not correlated with the hereditary dysfunction of CHEK2.
MDM4 gain, APC loss, and FBXW7 loss are the independent prognostic factors for extrohepatic metastasis-free survival after the operation for HCC[hepatocellular carcinoma ] and can be used to predict the risk of extrohepatic metastasis after the operation for HCC.
Authors present the structure of FBXW7 bound to the DISC1 phosphodegron motif and exploit this information to prove that disruption of the FBXW7-DISC1 complex results in a stabilization of DISC1.
FBXW7 is an essential tumor suppressor and is frequently inactivated in human cancer cells. In addition to genetic mutations, other mechanisms involving microRNA, long non-coding RNA, and specific oncogenic signaling pathways can inactivate FBXW7 functions in cancer cells. [review]
Low FBXW7 expression is associated with melanoma.
We showed that NONO interacts with the nuclear FBW7a isoform and its ubiquitination is regulated following modulation of the GSK3b kinase. Mutation of T428A/T432A within the degron impaired polyubiquitination upon FBW7a and GSK3b overexpression
F-box and WD repeat domain containing 7 (FBW7) silencing stabilized Snail protein and induced epithelial-to mesenchymal transition (EMT), and acquisition of migration and invasion properties in non-small cell lung cancer (NSCLC).
the results of the present study indicated the important function of miR27a in regulating the metastasis of breast cancer in a FBXW7dependent manner, and provide evidence for the potential application of miR27a in breast cancer therapy.
Brg1 is a bona fide ubiquitin substrate of SCF(FBW7). In keeping with a tumor suppressive role of FBW7 in human gastric cancer, we find an inverse correlation between FBW7 and Brg1 expression in human gastric cancer clinical samples. Mechanistically, we find that stabilization of Brg1 in gastric cancer cells suppresses E-cadherin expression, subsequently promoting gastric cancer metastasis.
Study showed that suppression of FBXW7 is associated with poor survival outcome in cholangiocarcinoma (CC) patients and was found to regulate the migration and self-renewal of CC cells through modulation of NOTCH1 as well as CDDP-induced apoptosis by MCL1 accumulation. These findings suggest that FBXW7 modulates the malignant potential-including metastasis and chemoresistance-of CC through two signals, NOTCH1 and MCL1.
Multivalent Interactions with Fbw7 and Pin1 Facilitate Recognition of c-Jun by the Fbw7.
FBXW7 is critical for RIG-I stabilization during antiviral responses.
Expression of miR-223 is negatively correlated with F-box and WD repeat domain-containing 7 (FBXW7) expression in cells and tissues.
FBXW7 conduction of tumour suppression was partly through degrading Snai1 directly for ubiquitylating regulation in NSCLC.
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.
Fbw7 mutations shifted cellular metabolism toward oxidative phosphorylation and caused context-specific metabolic vulnerabilities.
Myeloid-specific deficiency of FBXW7 can inhibit lung metastasis of B16F10 melanoma in mice, and the mechanism may be associated with regulation of MAM in the metastatic tumor lesions
Loss of Fbxw7 in the presence of BrafV600E mutation is consequential and sufficient to drive melanoma development.
A novel mouse line carrying a conditional knockin allele of a cancer-specific FBXW7 mutation was established for carcinogenesis study.
results thus suggest that Fbxw7 controls the transcription of MyRF target genes in various tissues through regulation of MyRF protein stability in a manner dependent on MyRF phosphorylation by GSK-3.
FBXW7 is markedly downregulated in the liver of obese mice. Mechanistically, FBXW7 directly binds to hepatokine fetuin-A to induce its ubiquitination and subsequent proteasomal degradation, comprising an important mechanism maintaining glucose homeostasis.
the regulatory crosstalk between KLF5, miR-29a, and Fbw7/CDC4 cooperatively promotes atherosclerotic development
found that Fbw7 loss caused activation of NF-kappaB signaling. Thus, FBW7 plays a protective role in acute intestinal inflammation by modulating the inflammatory response of NF-kappaB pathway.
EglN2 might act as an FBW7 ubiquitin ligase substrate contributing to the progression of triple negative breast cancer.
These findings highlight the molecular basis of Hajdu-Cheney syndrome (HCS) pathogenesis and provide clinical insights into potential targeted therapeutic strategies for skeletal disorders associated with the aberrant FBW7/NOTCH2 pathway as observed in patients with HCS.
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.
Fbxw7 suppresses KrasG12D-induced pancreatic tumorigenesis via a Yap-dependent mechanism.
Myoblast differentiation potential and muscle regeneration can be regulated by Fbxw7beta.
Study identifies a REV-ERBalpha post-translational regulatory circuit in which cyclin-dependent kinase 1 (CDK1) phosphorylation of REV-ERBalpha is recognized by the F-box protein, FBXW7alpha, to direct REV-ERBalpha degradation via the proteasome. Disruption of this CDK1-FBXW7-mediated REV-ERBalpha degradation pathway in mouse liver alters circadian rhythmicity, in particular amplitude, and whole-body lipid/glucose home...
Gene expression profiling reveals transcriptional regulation by Fbxw7/mTOR pathway in radiation-induced mouse thymic lymphomas.
Prion infection induced the expression of FBXW7 in brain.
FBXW7 facilitates nonhomologous end-joining via K63-linked polyubiquitylation of XRCC4 in tumor cells.
In mice, an unusually direct antagonism between an E3 ligase and a deubiquitinase, Fbw7 and Usp28, modulate intestinal homeostasis and cancer.
These data show that cell cycle-dependent mechanisms can control ciliary length through a CDK5-FBW7-NDE1 pathway.
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.
F-box and WD-40 domain protein 7
, F-box/WD repeat-containing protein 7
, F-box and WD-40 domain protein 7 (archipelago homolog, Drosophila)
, F-box protein FBW7
, F-box protein FBX30
, F-box protein SEL-10
, homolog of C elegans sel-10
, F-box and WD-40 domain protein 7, archipelago homolog
, F-box and WD-40 domain-containing protein 7
, F-box protein Fbxw6
, F-box-WD40 repeat protein 6
, f-box only protein 30