Gene Symbol: FBXW8
Description: F-box and WD repeat domain containing 8
Alias: FBW6, FBW8, FBX29, FBXO29, FBXW6, F-box/WD repeat-containing protein 8, F-box and WD-40 domain protein 8, F-box and WD-40 domain-containing protein 8, F-box only protein 29
Species: human
Products:     FBXW8

Top Publications

  1. Koch H, Zhang R, Verdoodt B, Bailey A, Zhang C, Yates J, et al. Large-scale identification of c-MYC-associated proteins using a combined TAP/MudPIT approach. Cell Cycle. 2007;6:205-17 pubmed
    ..Among them were 17 previously known c-MYC-interactors. Selected new c-MYC-associated proteins (DBC-1, FBX29, KU70, MCM7, Mi2-beta/CHD4, RNA Pol II, RFC2, RFC3, SV40 Large T Antigen, TCP1alpha, U5-116kD, ZNF281) were ..
  2. Huber C, Dias Santagata D, Glaser A, O Sullivan J, Brauner R, Wu K, et al. Identification of mutations in CUL7 in 3-M syndrome. Nat Genet. 2005;37:1119-24 pubmed
    ..CUL7 assembles an E3 ubiquitin ligase complex containing Skp1, Fbx29 (also called Fbw8) and ROC1 and promotes ubiquitination...
  3. Dias D, Dolios G, Wang R, Pan Z. CUL7: A DOC domain-containing cullin selectively binds Skp1.Fbx29 to form an SCF-like complex. Proc Natl Acad Sci U S A. 2002;99:16601-6 pubmed
    ..Remarkably, CUL7 assembles an SCF-ROC1-like E3 ubiquitin ligase complex consisting of Skp1, CUL7, the Fbx29 F-box protein, and ROC1. In contrast to CUL1 that binds Skp1 by itself, CUL7 interacts with the Skp1...
  4. Tsutsumi T, Kuwabara H, Arai T, Xiao Y, DeCaprio J. Disruption of the Fbxw8 gene results in pre- and postnatal growth retardation in mice. Mol Cell Biol. 2008;28:743-51 pubmed
    CUL7 binds to SKP1, RBX1, and FBXW8 to form a cullin-RING ligase, or an SKP1-cullin-F box protein complex. The targeted disruption of the Cul7 gene in mice results in significant reduction in embryo size and neonatal lethality...
  5. Litterman N, Ikeuchi Y, Gallardo G, O Connell B, Sowa M, Gygi S, et al. An OBSL1-Cul7Fbxw8 ubiquitin ligase signaling mechanism regulates Golgi morphology and dendrite patterning. PLoS Biol. 2011;9:e1001060 pubmed publisher
    ..Here, we report that the E3 ubiquitin ligase Cul7(Fbxw8) localizes to the Golgi complex in mammalian brain neurons...
  6. Xu X, Sarikas A, Dias Santagata D, Dolios G, Lafontant P, Tsai S, et al. The CUL7 E3 ubiquitin ligase targets insulin receptor substrate 1 for ubiquitin-dependent degradation. Mol Cell. 2008;30:403-14 pubmed publisher
    ..a pivotal growth-regulatory role played by the Cullin 7 (CUL7) E3 ubiquitin ligase complex containing the Fbw8-substrate-targeting subunit, Skp1, and the ROC1 RING finger protein...
  7. Okabe H, Lee S, Phuchareon J, Albertson D, McCormick F, Tetsu O. A critical role for FBXW8 and MAPK in cyclin D1 degradation and cancer cell proliferation. PLoS ONE. 2006;1:e128 pubmed
    ..is mediated by phosphorylation at Thr286 through the activity of the Ras/Raf/MEK/ERK cascade and the F-box protein FBXW8, which is an E3 ligase. The majority of FBXW8 is expressed in the cytoplasm during G1 and S phase...
  8. Lin P, Zhu L, Sun W, Yang Z, Sun H, Li D, et al. Prostate cancer cell proliferation is suppressed by microRNA-3160-5p via targeting of F-box and WD repeat domain containing 8. Oncol Lett. 2018;15:9436-9442 pubmed publisher
    ..was a negative association between the expression of miR-3160-5p and F-box and WD repeat domain containing 8 (Fbxw8) in prostate cancer DU145 cells...
  9. Bis J, DeCarli C, Smith A, van der Lijn F, Crivello F, Fornage M, et al. Common variants at 12q14 and 12q24 are associated with hippocampal volume. Nat Genet. 2012;44:545-51 pubmed publisher
    ..3 × 10(-11)) and at 12q24 near HRK-FBXW8 (rs7294919; P = 2.9 × 10(-11)). Remaining associations included one SNP at 2q24 within DPP4 (rs6741949; P = 2...

More Information


  1. Bulayeva K, Lesch K, Bulayev O, Walsh C, Glatt S, Gurgenova F, et al. Genomic structural variants are linked with intellectual disability. J Neural Transm (Vienna). 2015;122:1289-301 pubmed publisher
    ..for ID cases 2512 kb (500-6,472 kb) and for healthy control 682 kb (531-986 kb), including the genes MED13L, HRK, FBXW8, TESC, CDK2AP1 and SBNO1. Seven of 21 affected pedigree members displayed segmental deletions at 22q12...
  2. Scheufele F, Wolf B, Kruse M, Hartmann T, Lempart J, Mühlich S, et al. Evidence for a regulatory role of Cullin-RING E3 ubiquitin ligase 7 in insulin signaling. Cell Signal. 2014;26:233-239 pubmed publisher
    ..In vivo, heterozygosity of either Cul7 or Fbxw8, both key components of CRL7, resulted in elevated PI3 kinase/AKT activation in skeletal muscle tissue upon ..
  3. Wang H, Maitra A, Wang H. The emerging roles of F-box proteins in pancreatic tumorigenesis. Semin Cancer Biol. 2016;36:88-94 pubmed publisher
    ..on ?-TrCP (?-transducin repeat-containing protein) and two other prototypical mammalian F-box proteins, Fbxw7 and Fbxw8, in pancreatic tumorigenesis and progression...
  4. Wang J, Bogdanova N, Schürmann P, Park Simon T, Geffers R, Dork T. Assessment of a FBXW8 frameshift mutation, c.1312_1313delGT, in breast cancer patients and controls from Central Europe. Cancer Genet. 2018;220:38-43 pubmed publisher
    ..processes through ubiquitylation and subsequent degradation of target proteins, such as cyclin D1 as target of FBXW8. To investigate the spectrum of FBXW8 germ-line mutations in patients with breast cancer and healthy controls, we ..
  5. Halbach M, Stehning T, Damrath E, Jendrach M, Åžen N, BaÅŸak A, et al. Both ubiquitin ligases FBXW8 and PARK2 are sequestrated into insolubility by ATXN2 PolyQ expansions, but only FBXW8 expression is dysregulated. PLoS ONE. 2015;10:e0121089 pubmed publisher
    ..induction of the multi-subunit RING finger Skp1/Cul/F-box (SCF) type E3 ubiquitin-protein ligase complex component FBXW8 in global microarray profiling of ATXN2-expansion mouse cerebellum and demonstrated its role for ATXN2 degradation ..
  6. Guardavaccaro D, Frescas D, Dorrello N, Peschiaroli A, Multani A, Cardozo T, et al. Control of chromosome stability by the beta-TrCP-REST-Mad2 axis. Nature. 2008;452:365-9 pubmed publisher
    ..The high levels of REST or its truncated variants found in certain human tumours may contribute to cellular transformation by promoting genomic instability. ..
  7. Ponyeam W, Hagen T. Characterization of the Cullin7 E3 ubiquitin ligase--heterodimerization of cullin substrate receptors as a novel mechanism to regulate cullin E3 ligase activity. Cell Signal. 2012;24:290-5 pubmed publisher
    ..Similarly to Cul1, Cul7 interacts with Rbx1, however, only one F-box protein, Fbxw8, has been shown to bind to Cul7...
  8. Shi D, Tan Z, Lu R, Yang W, Zhang Y. MicroRNA-218 inhibits the proliferation of human choriocarcinoma JEG-3 cell line by targeting Fbxw8. Biochem Biophys Res Commun. 2014;450:1241-6 pubmed publisher
    ..In this study, we showed that miR-218 expression levels were decreased while Fbxw8 expression levels were increased in human choriocarcinoma cell lines, and identified Fbxw8 as a novel direct ..
  9. Yan J, Yan F, Li Z, Sinnott B, Cappell K, Yu Y, et al. The 3M complex maintains microtubule and genome integrity. Mol Cell. 2014;54:791-804 pubmed publisher
    ..We propose that CUL7, OBSL1, and CCDC8 proteins form a 3M complex that functions in maintaining microtubule and genome integrity and normal development. ..
  10. Tian X, Dai S, Sun J, Jin G, Jiang S, Meng F, et al. F-box protein FBXO22 mediates polyubiquitination and degradation of KLF4 to promote hepatocellular carcinoma progression. Oncotarget. 2015;6:22767-75 pubmed
    ..Therefore, our results suggest that FBXO22 might be a major regulator of HCC development through direct degradation of KLF4. ..
  11. Bae K, Yu D, Lee K, Yao K, Ryu J, Lim D, et al. Serine 347 Phosphorylation by JNKs Negatively Regulates OCT4 Protein Stability in Mouse Embryonic Stem Cells. Stem Cell Reports. 2017;9:2050-2064 pubmed publisher
    ..Moreover, phosphorylation of OCT4 induced binding of FBXW8, which reduced OCT4 protein stability and enhanced its proteasomal degradation...
  12. Fahlbusch F, Dawood Y, Hartner A, Menendez Castro C, Nögel S, Tzschoppe A, et al. Cullin 7 and Fbxw 8 expression in trophoblastic cells is regulated via oxygen tension: implications for intrauterine growth restriction?. J Matern Fetal Neonatal Med. 2012;25:2209-15 pubmed publisher
    The F-box protein Fbxw8 is a cofactor of Cullin 7 (Cul7), which regulates protein transfer to the proteasome and cell growth...
  13. Keutgens A, Zhang X, Shostak K, Robert I, Olivier S, Vanderplasschen A, et al. BCL-3 degradation involves its polyubiquitination through a FBW7-independent pathway and its binding to the proteasome subunit PSMB1. J Biol Chem. 2010;285:25831-40 pubmed publisher
    ..Thus, our data defined a unique motif of BCL-3 that is needed for its recruitment to the proteasome and identified PSMB1 as a key protein required for the proteasome-mediated degradation of a nuclear and oncogenic IkappaB protein. ..
  14. Skaar J, Florens L, Tsutsumi T, Arai T, Tron A, Swanson S, et al. PARC and CUL7 form atypical cullin RING ligase complexes. Cancer Res. 2007;67:2006-14 pubmed
    ..However, PARC fails to bind SKP1 or F-box proteins, including the CUL7-associated FBXW8. To examine the assembly of PARC- and CUL7-containing complexes, tandem affinity purification followed by ..
  15. Xu X, Keshwani M, Meyer K, Sarikas A, Taylor S, Pan Z. Identification of the degradation determinants of insulin receptor substrate 1 for signaling cullin-RING E3 ubiquitin ligase 7-mediated ubiquitination. J Biol Chem. 2012;287:40758-66 pubmed publisher
    ..The requirement of multisite phosphorylation and the N terminus of IRS1 for its turnover may ensure that complete IRS1 degradation occurs only when mTORC1 and S6K1 reach exceedingly high levels. ..
  16. Wang H, Chen Y, Lin P, Li L, Zhou G, Liu G, et al. The CUL7/F-box and WD repeat domain containing 8 (CUL7/Fbxw8) ubiquitin ligase promotes degradation of hematopoietic progenitor kinase 1. J Biol Chem. 2014;289:4009-17 pubmed publisher
    ..We found that the CUL7/Fbxw8 ubiquitin ligase targeted HPK1 for degradation via the 26 S proteasome...
  17. Lin P, Fu J, Zhao B, Lin F, Zou H, Liu L, et al. Fbxw8 is involved in the proliferation of human choriocarcinoma JEG-3 cells. Mol Biol Rep. 2011;38:1741-7 pubmed publisher
    b>Fbxw8 is the F-box component of a SCF-like E3 ubiquitin ligase complex. Mice lacking Fbxw8 exhibit pathological defects in placenta and embryo similar to fetal growth retardation, suggesting a role of Fbxw8 in placentation...
  18. Kimbrel E, Kung A. The F-box protein beta-TrCp1/Fbw1a interacts with p300 to enhance beta-catenin transcriptional activity. J Biol Chem. 2009;284:13033-44 pubmed publisher
  19. Lee K, Jeon Y, Kim H, Ryu J, Lim D, Jung S, et al. The CUG-translated WT1, not AUG-WT1, is an oncogene. Carcinogenesis. 2017;38:1228-1240 pubmed publisher
    ..on Ser62 and protected cugWT1 from proteasomal degradation induced by the F-box/WD repeat-containing protein 8 (FBXW8)...
  20. Li D, Liu S, Zhu L, Wang Y, Chen Y, Liu J, et al. FBXW8-dependent degradation of MRFAP1 in anaphase controls mitotic cell death. Oncotarget. 2017;8:97178-97186 pubmed publisher
    ..show, by using an immunoprecipitation-based proteomics screen, that MRFAP1 is an interactor of the F-box protein FBXW8. MRFAP1 is degraded by means of the ubiquitin ligase Cul7/FBXW8 during mitotic anaphase-telophase transition and ..
  21. Watanabe N, Arai H, Nishihara Y, Taniguchi M, Watanabe N, Hunter T, et al. M-phase kinases induce phospho-dependent ubiquitination of somatic Wee1 by SCFbeta-TrCP. Proc Natl Acad Sci U S A. 2004;101:4419-24 pubmed
    ..These results also establish the existence of a feedback loop between Cdc2 and Wee1A in somatic cells that depends on ubiquitination and protein degradation and ensures the rapid activation of Cdc2 when cells are ready to divide. ..
  22. Kong C, Samovski D, Srikanth P, Wainszelbaum M, Charron A, Liu J, et al. Ubiquitination and degradation of the hominoid-specific oncoprotein TBC1D3 is mediated by CUL7 E3 ligase. PLoS ONE. 2012;7:e46485 pubmed publisher
    ..Moreover, TBC1D3 recruits F-box 8 (Fbw8), the substrate recognition domain of CUL7 E3 ligase, in pull-down experiments and in an in vitro assay...
  23. Stein J, Medland S, Vasquez A, Hibar D, Senstad R, Winkler A, et al. Identification of common variants associated with human hippocampal and intracranial volumes. Nat Genet. 2012;44:552-61 pubmed publisher
    ..3; N = 15,782; P = 1.12 × 10(-12)). We also identified a suggestive association with total brain volume at rs10494373 within DDR2 (1q23.3; N = 6,500; P = 5.81 × 10(-7)). ..
  24. Busino L, Millman S, Scotto L, Kyratsous C, Basrur V, O CONNOR O, et al. Fbxw7?- and GSK3-mediated degradation of p100 is a pro-survival mechanism in multiple myeloma. Nat Cell Biol. 2012;14:375-85 pubmed publisher
    ..Thus, in multiple myeloma, Fbxw7? and GSK3 function as pro-survival factors through the control of p100 degradation. ..
  25. Wei S, Yang H, Chuang H, Yang J, Kulp S, Lu P, et al. A novel mechanism by which thiazolidinediones facilitate the proteasomal degradation of cyclin D1 in cancer cells. J Biol Chem. 2008;283:26759-70 pubmed publisher
    ..whereas no specific binding was noted with other F-box proteins examined, including Skp2, Fbw7, Fbx4, and Fbxw8. This finding represents the first evidence that cyclin D1 is targeted by beta-TrCP...
  26. Yoon M. The Role of Mammalian Target of Rapamycin (mTOR) in Insulin Signaling. Nutrients. 2017;9: pubmed publisher
    ..factor receptor-bound protein 10 (Grb10), insulin receptor substrate (IRS-1), F-box/WD repeat-containing protein 8 (Fbw8), and insulin like growth factor 1 receptor/insulin receptor (IGF-IR/IR)...
  27. Shi D, Zhang Y, Lu R, Zhang Y. The long non-coding RNA MALAT1 interacted with miR-218 modulates choriocarcinoma growth by targeting Fbxw8. Biomed Pharmacother. 2018;97:543-550 pubmed publisher
    ..What is more, miR-218-mediated Fbxw8 regulation was required for MALAT1-induced choriocarcinoma cell proliferation...