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proteins. Page last changed on 14 Mar 2013.
F-box protein 4
Fbx4, F-box protein FBX4
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 the 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 belongs to the Fbxs class. Alternative splicing of this gene generates 2 transcript variants. [provided by RefSeq, Jul 2008] (from
NCBI)
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Papers using
Fbx4
antibodies
Phosphorylation by Akt1 promotes cytoplasmic localization of Skp2 and impairs APCCdh1-mediated Skp2 destruction
Supplier
In PLoS ONE, 2008
... Rabbit antibodies: Emi1, Millipore; Fbx4, Rockland (Gilbertsville, PA); Fbx7, Fbx31, ...
Papers on
Fbx4
Computationally Designed Peptide Inhibitors of the Ubiquitin E3 Ligase SCF(Fbx4).
New
Boulder, United States. In Chembiochem, 04 Apr 2013
A structure-based computational approach was used to rationally design peptide inhibitors that can target an E3 ligase (SCF(Fbx4) )-substrate (TRF1) interface and subsequent ubiquitylation.
Multiplex mutation screening by mass spectrometry in gastrointestinal stromal tumours.
New
Seoul, South Korea. In Pathology, Aug 2012
A substitution in FBX4 exon 1 (S8R), representing a germline single-nucleotide polymorphism, was observed in a case with KIT exon 11 missense mutation.
The Fbx4 tumor suppressor regulates cyclin D1 accumulation and prevents neoplastic transformation.
GeneRIF
Philadelphia, United States. In Mol Cell Biol, 2011
Fbx4 expression is essential for cell homeostasis in somatic cells. Fbx4 ablation predisposes mice to multiple tumor phenotypes, with concomitant cyclin D1 deregulation and nuclear accumulation
Phosphorylation-dependent regulation of SCF(Fbx4) dimerization and activity involves a novel component, 14-3-3ɛ.
GeneRIF
Philadelphia, United States. In Oncogene, 2011
14-3-3varepsilon binds to Ser12-phosphorylated Fbx4 to mediate dimerization and function.
Immunohistochemical and molecular markers in breast phyllodes tumors.
Portland, United States. In Appl Immunohistochem Mol Morphol, 2011
Mutational analysis revealed an S8R substitution in FBX4 (an E3 ubiquitin ligase) in 3 cases: 1 benign and 2 borderline.
The influence of surface microroughness and hydrophilicity of titanium on the up-regulation of TGFβ/BMP signalling in osteoblasts.
Gold Coast, Australia. In Biomaterials, 2011
Several other genes associated with the functionally important mechanisms relevant to bone healing, such as Wnt signalling (CTNNA1, FBX4, FZD6), angiogenesis (KDR), osteoclastogenesis (HSF2, MCL1) and proteolysis (HEXB, TPP1), were also differentially regulated.
Nuclear cyclin D1/CDK4 kinase regulates CUL4 expression and triggers neoplastic growth via activation of the PRMT5 methyltransferase.
Impact
Philadelphia, United States. In Cancer Cell, 2010
Importantly, human cancers harboring mutations in Fbx4, the cyclin D1 E3 ligase, exhibit nuclear cyclin D1 accumulation and increased PRMT5 activity.
Structural basis of dimerization-dependent ubiquitination by the SCF(Fbx4) ubiquitin ligase.
GeneRIF
Farmington, United States. In J Biol Chem, 2010
Biochemical studies indicate that both the N-terminal domain and a loop connecting the linker and C-terminal domain of Fbx4 are critical for the dimerization and activation of the protein.
alphaB-crystallin is mutant B-RAF regulated and contributes to cyclin D1 turnover in melanocytic cells.
Philadelphia, United States. In Pigment Cell Melanoma Res, 2010
Recently, a second F-box protein cofactor was identified, alphaB-crystallin, that binds Fbx4 and promotes cyclin D1 degradation.
Structural basis of selective ubiquitination of TRF1 by SCFFbx4.
GeneRIF
Ann Arbor, United States. In Dev Cell, 2010
results reveal an atypical small GTPase domain within Fbx4 as a substrate-binding motif for SCF(Fbx4) and uncover a mechanism for selective ubiquitination and degradation of TRF1 in telomere homeostasis control
Telomeric TuRF1 wars.
Boston, United States. In Dev Cell, 2010
Work from Zeng et al. (2010) now reveals in atomic detail how a battle between the SCF(FBX4) ubiquitin ligase and the shelterin component TIN2 controls TRF1 abundance and telomere length homeostasis.
Lysine 269 is essential for cyclin D1 ubiquitylation by the SCF(Fbx4/alphaB-crystallin) ligase and subsequent proteasome-dependent degradation.
GeneRIF
Philadelphia, United States. In Oncogene, 2010
Lysine 269 is essential for cyclin D1 ubiquitylation by the SCF(Fbx4/alphaB-crystallin) ligase.
GNL3L stabilizes the TRF1 complex and promotes mitotic transition.
Houston, United States. In J Cell Biol, 2009
GNL3L binds TRF1 in the nucleoplasm and is capable of promoting the homodimerization and telomeric association of TRF1, preventing promyelocytic leukemia body recruitment of telomere-bound TRF1, and stabilizing TRF1 protein by inhibiting its ubiquitylation and binding to FBX4, an E3 ubiquitin ligase for TRF1.
SCF(Fbx4/alphaB-crystallin) E3 ligase: when one is not enough.
Review
Philadelphia, United States. In Cell Cycle, 2008
Cyclin D1 proteolysis requires phosphorylation by GSK3beta at Thr-286; additional work recently established that p286-D1 is a substrate for the SCF(Fbx4/alphaB-crystallin) E3 ligase.
Mutations in Fbx4 inhibit dimerization of the SCF(Fbx4) ligase and contribute to cyclin D1 overexpression in human cancer.
Impact
GeneRIF
Philadelphia, United States. In Cancer Cell, 2008
Mutations in Fbx4 inhibit dimerization of the SCF(Fbx4) ligase and contribute to cyclin D1 overexpression in human cancer.
