FBXW7

Summary

Gene Symbol: FBXW7
Description: F-box and WD repeat domain containing 7
Alias: AGO, CDC4, FBW6, FBW7, FBX30, FBXO30, FBXW6, SEL-10, SEL10, hAgo, hCdc4, F-box/WD repeat-containing protein 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 FBW7, F-box protein FBX30, F-box protein SEL-10, archipelago, homolog of C elegans sel-10
Species: human
Products:     FBXW7

Top Publications

  1. Welcker M, Clurman B. The SV40 large T antigen contains a decoy phosphodegron that mediates its interactions with Fbw7/hCdc4. J Biol Chem. 2005;280:7654-8 pubmed
    ..Here we report that LT binds directly to Fbw7, the substrate recognition component of the SCF(Fbw7) ubiquitin ligase and a human tumor suppressor...
  2. Hao B, Oehlmann S, Sowa M, Harper J, Pavletich N. Structure of a Fbw7-Skp1-cyclin E complex: multisite-phosphorylated substrate recognition by SCF ubiquitin ligases. Mol Cell. 2007;26:131-43 pubmed
    ..Biochemical data indicate that the closely related yeast SCF(Cdc4) complex recognizes the multisite phosphorylated Sic1 substrate similarly and identify three doubly phosphorylated ..
  3. Iwatsuki M, Mimori K, Ishii H, Yokobori T, Takatsuno Y, Sato T, et al. Loss of FBXW7, a cell cycle regulating gene, in colorectal cancer: clinical significance. Int J Cancer. 2010;126:1828-1837 pubmed publisher
    This study focused on a cell cycle regulatory gene, FBXW7, which ubiquitinates c-Myc and cyclin E and promotes exit from the cell cycle...
  4. Zhao D, Zheng H, Zhou Z, Chen C. The Fbw7 tumor suppressor targets KLF5 for ubiquitin-mediated degradation and suppresses breast cell proliferation. Cancer Res. 2010;70:4728-38 pubmed publisher
    ..Mutation of the critical S303 residue in the KLF5 Cdc4 phospho-degrons motif ((303)SPPSS) abolishes the protein interaction, ubiquitination, and degradation by Fbw7...
  5. Mao J, Kim I, Wu D, Climent J, Kang H, DelRosario R, et al. FBXW7 targets mTOR for degradation and cooperates with PTEN in tumor suppression. Science. 2008;321:1499-502 pubmed publisher
    ..that mTOR is targeted for ubiquitination and consequent degradation by binding to the tumor suppressor protein FBXW7. Human breast cancer cell lines and primary tumors showed a reciprocal relation between loss of FBXW7 and deletion ..
  6. Grim J, Gustafson M, Hirata R, Hagar A, Swanger J, Welcker M, et al. Isoform- and cell cycle-dependent substrate degradation by the Fbw7 ubiquitin ligase. J Cell Biol. 2008;181:913-20 pubmed publisher
    The SCF(FBW7) ubiquitin ligase degrades proteins involved in cell division, growth, and differentiation and is commonly mutated in cancers...
  7. Mo J, Ann E, Yoon J, Jung J, Choi Y, Kim H, et al. Serum- and glucocorticoid-inducible kinase 1 (SGK1) controls Notch1 signaling by downregulation of protein stability through Fbw7 ubiquitin ligase. J Cell Sci. 2011;124:100-12 pubmed publisher
    ..Notch1 and Fbw7 mutations both lead the activation of the Notch1 pathway and are found in the majority of patients with the ..
  8. Minella A, Welcker M, Clurman B. Ras activity regulates cyclin E degradation by the Fbw7 pathway. Proc Natl Acad Sci U S A. 2005;102:9649-54 pubmed
    The Skp1-Cullin1 F-box protein-Fbw7 ubiquitin ligase regulates phosphorylation-dependent cyclin E degradation, and disruption of this pathway is associated with genetic instability and tumorigenesis...
  9. Kanei Ishii C, Nomura T, Takagi T, Watanabe N, Nakayama K, Ishii S. Fbxw7 acts as an E3 ubiquitin ligase that targets c-Myb for nemo-like kinase (NLK)-induced degradation. J Biol Chem. 2008;283:30540-8 pubmed publisher
    ..Here, we report that Fbxw7, the F-box protein of an SCF complex, targets c-Myb for degradation in a Wnt-1- and NLK-dependent manner...

More Information

Publications73

  1. Inuzuka H, Shaik S, Onoyama I, Gao D, Tseng A, Maser R, et al. SCF(FBW7) regulates cellular apoptosis by targeting MCL1 for ubiquitylation and destruction. Nature. 2011;471:104-9 pubmed publisher
    ..Loss of FBW7, which encodes a tumour-suppressor protein, is frequently found in various types of human cancer, including breast ..
  2. Baldus C, Thibaut J, Goekbuget N, Stroux A, Schlee C, Mossner M, et al. Prognostic implications of NOTCH1 and FBXW7 mutations in adult acute T-lymphoblastic leukemia. Haematologica. 2009;94:1383-90 pubmed publisher
    ..Here we have investigated the prognostic impact of mutations in the NOTCH1 pathway, in particular, the NOTCH1 and FBXW7 genes, in a large cohort of adult patients with T-lymphoblastic leukemia (n=126)...
  3. Chen M, Chen C, Chuang H, Kulp S, Teng C, Chen C. Novel mechanism by which histone deacetylase inhibitors facilitate topoisomerase II? degradation in hepatocellular carcinoma cells. Hepatology. 2011;53:148-59 pubmed publisher
    ..Furthermore, we identified Fbw7, a Csn5-interacting F-box protein, as the E3 ligase that targeted topoII? for degradation...
  4. Ekholm Reed S, Spruck C, Sangfelt O, van Drogen F, Mueller Holzner E, Widschwendter M, et al. Mutation of hCDC4 leads to cell cycle deregulation of cyclin E in cancer. Cancer Res. 2004;64:795-800 pubmed
    b>hCDC4, the gene that encodes the F-box protein responsible for targeting cyclin E for ubiquitin-mediated proteolysis, has been found to be mutated in a number of primary cancers and cancer-derived cell lines...
  5. Welcker M, Clurman B. FBW7 ubiquitin ligase: a tumour suppressor at the crossroads of cell division, growth and differentiation. Nat Rev Cancer. 2008;8:83-93 pubmed
    b>FBW7 (F-box and WD repeat domain-containing 7) is the substrate recognition component of an evolutionary conserved SCF (complex of SKP1, CUL1 and F-box protein)-type ubiquitin ligase...
  6. Tan Y, Sangfelt O, Spruck C. The Fbxw7/hCdc4 tumor suppressor in human cancer. Cancer Lett. 2008;271:1-12 pubmed publisher
    Fbxw7/hCdc4 is a member of the F-box family of proteins, which function as interchangeable substrate recognition components of the SCF ubiquitin ligases...
  7. Zhang W, Koepp D. Fbw7 isoform interaction contributes to cyclin E proteolysis. Mol Cancer Res. 2006;4:935-43 pubmed
    ..The putative tumor-suppressor protein Fbw7 (hAgo/hCdc4) is a specificity factor for the Skp1-Cul1-F-box protein ubiquitin ligase complex and targets a number of proto-..
  8. van Drogen F, Sangfelt O, Malyukova A, Matskova L, Yeh E, Means A, et al. Ubiquitylation of cyclin E requires the sequential function of SCF complexes containing distinct hCdc4 isoforms. Mol Cell. 2006;23:37-48 pubmed
    ..targeted for proteasomal degradation by phosphorylation-dependent multiubiquitylation via the ubiquitin ligase SCF(hCdc4)...
  9. Thompson B, Buonamici S, Sulis M, Palomero T, Vilimas T, Basso G, et al. The SCFFBW7 ubiquitin ligase complex as a tumor suppressor in T cell leukemia. J Exp Med. 2007;204:1825-35 pubmed
    ..We report that the E3 ligase FBW7 targets NOTCH1 for ubiquitination and degradation...
  10. 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
    b>Fbxw7? is a member of the F-box family of proteins, which function as the substrate-targeting subunits of SCF (Skp1/Cul1/F-box protein) ubiquitin ligase complexes...
  11. Zhou Z, Tu K, Zhang J, Zheng X, Gao J, Yao Y, et al. [Expression of Fbxw7 and its correlation with cell proliferation in human hepatocellular carcinoma]. Xi Bao Yu Fen Zi Mian Yi Xue Za Zhi. 2012;28:1303-6 pubmed
    To observe the expression of Fbxw7 and explore its correlation with cell proliferation of hepatocellular carcinoma (HCC)...
  12. Yan T, Wunder J, Gokgoz N, Seto K, Bell R, Andrulis I. hCDC4 variation in osteosarcoma. Cancer Genet Cytogenet. 2006;169:138-42 pubmed
    The hCDC4 gene (also known as Fbw7 or Archipelago) encodes an F-box protein that is responsible for targeting cyclin E for Skp1-cullin-F box protein (SCF) ubiquitination and proteosomal degradation...
  13. Cizmecioglu O, Krause A, Bahtz R, Ehret L, Malek N, Hoffmann I. Plk2 regulates centriole duplication through phosphorylation-mediated degradation of Fbxw7 (human Cdc4). J Cell Sci. 2012;125:981-92 pubmed publisher
    ..Here, we show that Plk2 directly targets the F-box protein F-box/WD repeat-containing protein 7 (Fbxw7), which is a regulator of the ubiquitin-mediated degradation of cyclin E...
  14. Wei W, Jin J, Schlisio S, Harper J, Kaelin W. The v-Jun point mutation allows c-Jun to escape GSK3-dependent recognition and destruction by the Fbw7 ubiquitin ligase. Cancer Cell. 2005;8:25-33 pubmed
    ..c-Myc, we report here that phosphorylation of c-Jun by GSK3 creates a high-affinity binding site for the E3 ligase Fbw7, which targets c-Jun for polyubiquitination and proteasomal degradation...
  15. Welcker M, Orian A, Jin J, Grim J, Grim J, Harper J, et al. The Fbw7 tumor suppressor regulates glycogen synthase kinase 3 phosphorylation-dependent c-Myc protein degradation. Proc Natl Acad Sci U S A. 2004;101:9085-90 pubmed
    ..Myc proteins regulate cell growth and division and are implicated in a wide range of human cancers. We show here that Fbw7, a component of the SCF(Fbw7) ubiquitin ligase and a tumor suppressor, promotes proteasome-dependent c-Myc turnover ..
  16. Rajagopalan H, Jallepalli P, Rago C, Velculescu V, Kinzler K, Vogelstein B, et al. Inactivation of hCDC4 can cause chromosomal instability. Nature. 2004;428:77-81 pubmed
    ..Here we report the identification of mutations in hCDC4 (also known as Fbw7 or Archipelago) in both human colorectal cancers and their precursor lesions...
  17. Larson Gedman A, Chen Q, Kugel Desmoulin S, Ge Y, LaFiura K, Haska C, et al. The impact of NOTCH1, FBW7 and PTEN mutations on prognosis and downstream signaling in pediatric T-cell acute lymphoblastic leukemia: a report from the Children's Oncology Group. Leukemia. 2009;23:1417-25 pubmed publisher
    We explored the impact of mutations in the NOTCH1, FBW7 and PTEN genes on prognosis and downstream signaling in a well-defined cohort of 47 patients with pediatric T-cell acute lymphoblastic leukemia (T-ALL)...
  18. Akhoondi S, Sun D, von der Lehr N, Apostolidou S, Klotz K, Maljukova A, et al. FBXW7/hCDC4 is a general tumor suppressor in human cancer. Cancer Res. 2007;67:9006-12 pubmed
    ..b>Fbxw7 (or hCdc4), a member of the F-box family of proteins, which are substrate recognition components of the ..
  19. Olson B, Hock M, Ekholm Reed S, Wohlschlegel J, Dev K, Kralli A, et al. SCFCdc4 acts antagonistically to the PGC-1alpha transcriptional coactivator by targeting it for ubiquitin-mediated proteolysis. Genes Dev. 2008;22:252-64 pubmed publisher
    ..We identified SCF(Cdc4) as an E3 ubiquitin ligase that regulates PGC-1alpha through ubiquitin-mediated proteolysis...
  20. Sancho R, Jandke A, Davis H, Diefenbacher M, Tomlinson I, Behrens A. F-box and WD repeat domain-containing 7 regulates intestinal cell lineage commitment and is a haploinsufficient tumor suppressor. Gastroenterology. 2010;139:929-41 pubmed publisher
    The E3 ubiquitin ligase F-box and WD repeat domain-containing 7 (Fbw7) degrades several proto-oncogenes including c-Myc, cyclinE, Notch1, and c-Jun...
  21. Gupta Rossi N, Le Bail O, Gonen H, Brou C, Logeat F, Six E, et al. Functional interaction between SEL-10, an F-box protein, and the nuclear form of activated Notch1 receptor. J Biol Chem. 2001;276:34371-8 pubmed
    ..SEL-10, an F-box protein of the Cdc4 family, was isolated in a genetic screen for Lin12/Notch-negative regulators in Caenorhabditis elegans...
  22. Strohmaier H, Spruck C, Kaiser P, Won K, Sangfelt O, Reed S. Human F-box protein hCdc4 targets cyclin E for proteolysis and is mutated in a breast cancer cell line. Nature. 2001;413:316-22 pubmed
    ..The gene encoding hCdc4 was found to be mutated in a cell line derived from breast cancer that expressed extremely high levels of cyclin E. ..
  23. Cheng Y, Chen G, Martinka M, Ho V, Li G. Prognostic significance of Fbw7 in human melanoma and its role in cell migration. J Invest Dermatol. 2013;133:1794-802 pubmed publisher
    The E3 ubiquitin ligase Fbw7 (F-box and WD repeat domain-containing 7) is broadly considered as a tumor suppressor because of its role in the turnover of several well-known oncoproteins...
  24. Ye X, Nalepa G, Welcker M, Kessler B, Spooner E, Qin J, et al. Recognition of phosphodegron motifs in human cyclin E by the SCF(Fbw7) ubiquitin ligase. J Biol Chem. 2004;279:50110-9 pubmed
    Turnover of cyclin E is controlled by SCF(Fbw7). Three isoforms of Fbw7 are produced by alternative splicing...
  25. Yada M, Hatakeyama S, Kamura T, Nishiyama M, Tsunematsu R, Imaki H, et al. Phosphorylation-dependent degradation of c-Myc is mediated by the F-box protein Fbw7. EMBO J. 2004;23:2116-25 pubmed
    ..We now show that the F-box protein Fbw7 interacts with and thereby destabilizes c-Myc in a manner dependent on phosphorylation of MB1...
  26. Wang Y, Liu Y, Lu J, Zhang P, Wang Y, Xu Y, et al. Rapamycin inhibits FBXW7 loss-induced epithelial-mesenchymal transition and cancer stem cell-like characteristics in colorectal cancer cells. Biochem Biophys Res Commun. 2013;434:352-6 pubmed publisher
    ..In this study, we explore whether FBXW7 plays any role in metastatic process...
  27. Park M, Taki T, Oda M, Watanabe T, Yumura Yagi K, Kobayashi R, et al. FBXW7 and NOTCH1 mutations in childhood T cell acute lymphoblastic leukaemia and T cell non-Hodgkin lymphoma. Br J Haematol. 2009;145:198-206 pubmed publisher
    Mutation analysis of FBXW7 and NOTCH1 genes was performed in 55 T cell acute lymphoblastic leukaemia (T-ALL) and 14 T cell non-Hodgkin lymphoma (T-NHL) patients who were treated on the Japan Association of Childhood Leukaemia Study (..
  28. Spruck C, Strohmaier H, Sangfelt O, Müller H, Hubalek M, Muller Holzner E, et al. hCDC4 gene mutations in endometrial cancer. Cancer Res. 2002;62:4535-9 pubmed
    ..profile of expression is the result of periodic transcription and ubiquitin-mediated proteolysis directed by SCF(hCdc4)...
  29. Gu Z, Mitsui H, Inomata K, Honda M, Endo C, Sakurada A, et al. The methylation status of FBXW7 beta-form correlates with histological subtype in human thymoma. Biochem Biophys Res Commun. 2008;377:685-688 pubmed publisher
    b>FBXW7 is reported to be a tumor suppressor gene, and the functional inactivation of FBXW7 has been reported in various human tumors...
  30. Li J, Pauley A, Myers R, Shuang R, Brashler J, Yan R, et al. SEL-10 interacts with presenilin 1, facilitates its ubiquitination, and alters A-beta peptide production. J Neurochem. 2002;82:1540-8 pubmed
    ..SEL-10 protein is a homologue of yeast Cdc4, a member of the SCF (Skp1-Cdc53/CUL1-F-box protein) E2-E3 ubiquitin ligase family...
  31. Onoyama I, Suzuki A, Matsumoto A, Tomita K, Katagiri H, Oike Y, et al. Fbxw7 regulates lipid metabolism and cell fate decisions in the mouse liver. J Clin Invest. 2011;121:342-54 pubmed publisher
    ..The F-box family member F-box- and WD repeat domain-containing 7 (Fbxw7; also known as Fbw7, SEL-10, hCdc4, and hAgo) targets for degradation proteins with wide-ranging functions, and ..
  32. Akhoondi S, Lindstrom L, Widschwendter M, Corcoran M, Bergh J, Spruck C, et al. Inactivation of FBXW7/hCDC4-? expression by promoter hypermethylation is associated with favorable prognosis in primary breast cancer. Breast Cancer Res. 2010;12:R105 pubmed publisher
    Mutational inactivation of the FBXW7/hCDC4 tumor suppressor gene (TSG) is common in many cancer types, but infrequent in breast cancers. This study investigates the presence and impact of FBXW7/hCDC4 promoter methylation in breast cancer...
  33. Suo J, Snider S, Mills G, Creighton C, Chen A, Schiff R, et al. Int6 regulates both proteasomal degradation and translation initiation and is critical for proper formation of acini by human mammary epithelium. Oncogene. 2011;30:724-36 pubmed publisher
    ..Our data further show that Int6 binds SRC3 and its ubiquitin ligase Fbw7, thus perhaps mediating the interaction between SRC3-Fbw7 and proteasomes...
  34. Bengoechea Alonso M, Ericsson J. A phosphorylation cascade controls the degradation of active SREBP1. J Biol Chem. 2009;284:5885-95 pubmed publisher
    ..Phosphorylation of Thr-426 and Ser-430 in SREBP1a creates a docking site for the ubiquitin ligase Fbw7, resulting in the degradation of the transcription factor...
  35. Kwon Y, Kim I, Wu D, Lu J, Stock W, Liu Y, et al. Pten regulates Aurora-A and cooperates with Fbxw7 in modulating radiation-induced tumor development. Mol Cancer Res. 2012;10:834-44 pubmed publisher
    ..Here, we show that Aurora-A is targeted for ubiquitination and subsequent degradation by the F-box protein FBXW7 in a process that is regulated by GSK3?...
  36. Matsumoto A, Tateishi Y, Onoyama I, Okita Y, Nakayama K, Nakayama K. Fbxw7? resides in the endoplasmic reticulum membrane and protects cells from oxidative stress. Cancer Sci. 2011;102:749-55 pubmed publisher
    Oxidative stress has been implicated in cancer initiation and progression. Fbxw7 (also known as Fbw7, SEL-10, hCdc4, or hAgo) is the F-box protein subunit of an Skp1-Cul1-F-box (SCF)-type ubiquitin ligase complex that plays a central ..
  37. Sangfelt O, Cepeda D, Malyukova A, van Drogen F, Reed S. Both SCF(Cdc4alpha) and SCF(Cdc4gamma) are required for cyclin E turnover in cell lines that do not overexpress cyclin E. Cell Cycle. 2008;7:1075-82 pubmed
    ..of cyclin E is regulated by phosphorylation and the activity of the ubiquitin ligase SCF(Cdc4) (also known as SCF(Fbw7))...
  38. Sundqvist A, Bengoechea Alonso M, Ye X, Lukiyanchuk V, Jin J, Harper J, et al. Control of lipid metabolism by phosphorylation-dependent degradation of the SREBP family of transcription factors by SCF(Fbw7). Cell Metab. 2005;1:379-91 pubmed
    ..Here, we identify a phosphodegron in SREBP1a that serves as a recognition motif for the SCF(Fbw7) ubiquitin ligase...
  39. Wu G, Lyapina S, Das I, Li J, Gurney M, Pauley A, et al. SEL-10 is an inhibitor of notch signaling that targets notch for ubiquitin-mediated protein degradation. Mol Cell Biol. 2001;21:7403-15 pubmed
    ..Thus, SEL-10 functions to promote the ubiquitination of Notch proteins; however, the fates of these proteins may differ. ..
  40. Koepp D, Schaefer L, Ye X, Keyomarsi K, Chu C, Harper J, et al. Phosphorylation-dependent ubiquitination of cyclin E by the SCFFbw7 ubiquitin ligase. Science. 2001;294:173-7 pubmed
    ..b>Fbw7 associates specifically with phosphorylated cyclin E, and SCFFbw7 catalyzes cyclin E ubiquitination in vitro...
  41. Liu N, Li H, Li S, Shen M, Xiao N, Chen Y, et al. The Fbw7/human CDC4 tumor suppressor targets proproliferative factor KLF5 for ubiquitination and degradation through multiple phosphodegron motifs. J Biol Chem. 2010;285:18858-67 pubmed publisher
    ..However, the mechanisms regulating protein stability remain poorly understood. In this study, the tumor suppressor Fbw7, a component of the SCF complex (SCF(Fbw7)) E3 ubiquitin ligase, specifically promoted the degradation and ..
  42. Ibusuki M, Yamamoto Y, Shinriki S, Ando Y, Iwase H. Reduced expression of ubiquitin ligase FBXW7 mRNA is associated with poor prognosis in breast cancer patients. Cancer Sci. 2011;102:439-45 pubmed publisher
    b>FBXW7 is a cell cycle regulatory gene that ubiquitinates positive cell cycle regulators such as c-Myc and cyclin E, allowing for cell cycle exit...
  43. Moberg K, Bell D, Wahrer D, Haber D, Hariharan I. Archipelago regulates Cyclin E levels in Drosophila and is mutated in human cancer cell lines. Nature. 2001;413:311-6 pubmed
    ..In a screen for Drosophila mutants that display increased cell proliferation, we identified archipelago, a gene encoding a protein with an F-box and seven tandem WD (tryptophan-aspartic acid) repeats...
  44. King B, Trimarchi T, Reavie L, Xu L, Mullenders J, Ntziachristos P, et al. The ubiquitin ligase FBXW7 modulates leukemia-initiating cell activity by regulating MYC stability. Cell. 2013;153:1552-66 pubmed publisher
    ..One such recurrent mutation targets the binding pocket of the ubiquitin ligase Fbxw7. Missense FBXW7 mutations are prevalent in various tumors, including T cell acute lymphoblastic leukemia (T-ALL)...
  45. Nateri A, Riera Sans L, Da Costa C, Behrens A. The ubiquitin ligase SCFFbw7 antagonizes apoptotic JNK signaling. Science. 2004;303:1374-8 pubmed
    ..We report that in neurons the stability of c-Jun is regulated by the E3 ligase SCF(Fbw7), which ubiquitinates phosphorylated c-Jun and facilitates c-Jun degradation...
  46. Lerner M, Lundgren J, Akhoondi S, Jahn A, Ng H, Akbari Moqadam F, et al. MiRNA-27a controls FBW7/hCDC4-dependent cyclin E degradation and cell cycle progression. Cell Cycle. 2011;10:2172-83 pubmed
    The F-box protein FBW7/hCDC4 is a tumor suppressor that acts as the substrate recognition component of an SCF ubiquitin ligase that targets numerous oncoproteins for proteasomal degradation...
  47. Oberg C, Li J, Pauley A, Wolf E, Gurney M, Lendahl U. The Notch intracellular domain is ubiquitinated and negatively regulated by the mammalian Sel-10 homolog. J Biol Chem. 2001;276:35847-53 pubmed
    ..In conclusion, these data reveal the importance of ubiquitination and proteasome-mediated degradation for the activity and turnover of Notch ICs, and demonstrate that mSel-10 plays a key role in this process. ..
  48. Bengoechea Alonso M, Ericsson J. Tumor suppressor Fbxw7 regulates TGF? signaling by targeting TGIF1 for degradation. Oncogene. 2010;29:5322-8 pubmed publisher
    ..The tumor suppressor Fbxw7 is the substrate-recognition factor of a ubiquitin ligase that targets multiple proteins for degradation, ..
  49. Welcker M, Clurman B. Fbw7/hCDC4 dimerization regulates its substrate interactions. Cell Div. 2007;2:7 pubmed
    The Fbw7 ubiquitin ligase promotes the rapid degradation of several important oncogenes, such as cyclin E, c-Myc, c-Jun, and Notch. The two fission yeast homologs of Fbw7, pop1 and pop2, have previously been shown to dimerize...
  50. O Neil J, Grim J, Strack P, Rao S, Tibbitts D, Winter C, et al. FBW7 mutations in leukemic cells mediate NOTCH pathway activation and resistance to gamma-secretase inhibitors. J Exp Med. 2007;204:1813-24 pubmed
    ..6%) primary T-ALL samples harbored either a mutation or homozygous deletion of the gene FBW7, a ubiquitin ligase implicated in NICD turnover...
  51. Calhoun E, Jones J, Ashfaq R, Adsay V, Baker S, Valentine V, et al. BRAF and FBXW7 (CDC4, FBW7, AGO, SEL10) mutations in distinct subsets of pancreatic cancer: potential therapeutic targets. Am J Pathol. 2003;163:1255-60 pubmed
    ..the mutational status of the serine/threonine kinase BRAF and the cyclin E regulator FBXW7 (CDC4, FBW7, AGO, SEL10) related to two distinct pancreatic carcinoma subsets: the medullary KRAS2-wild-type and the cyclin E ..
  52. Yokobori T, Mimori K, Iwatsuki M, Ishii H, Onoyama I, Fukagawa T, et al. p53-Altered FBXW7 expression determines poor prognosis in gastric cancer cases. Cancer Res. 2009;69:3788-94 pubmed publisher
    A molecular target associated with the progression of gastric cancer has not yet been uncovered. FBXW7 is a tumor suppressor gene transcriptionally controlled by p53 that plays a role in the regulation of cell cycle exit and reentry via ..
  53. Asnafi V, Buzyn A, Le Noir S, Baleydier F, Simon A, Beldjord K, et al. NOTCH1/FBXW7 mutation identifies a large subgroup with favorable outcome in adult T-cell acute lymphoblastic leukemia (T-ALL): a Group for Research on Adult Acute Lymphoblastic Leukemia (GRAALL) study. Blood. 2009;113:3918-24 pubmed publisher
    ..NOTCH1 and/or FBXW7 mutations both lead to activation of the NOTCH1 pathway and are among the most frequent mutations in T-ALL...
  54. Bonetti P, Davoli T, Sironi C, Amati B, Pelicci P, Colombo E. Nucleophosmin and its AML-associated mutant regulate c-Myc turnover through Fbw7 gamma. J Cell Biol. 2008;182:19-26 pubmed publisher
    ..Because Fbw7 induces degradation of other growth-promoting proteins, the NPM-Fbw7 interaction emerges as a central tumor ..
  55. Tu K, Yang W, Li C, Zheng X, Lu Z, Guo C, et al. Fbxw7 is an independent prognostic marker and induces apoptosis and growth arrest by regulating YAP abundance in hepatocellular carcinoma. Mol Cancer. 2014;13:110 pubmed publisher
    The E3 ubiquitin ligase Fbxw7 functions as a general tumor suppressor by targeting several well-known oncoproteins for ubiquitination and proteasomal degradation...
  56. Welcker M, Orian A, Grim J, Grim J, Eisenman R, Clurman B. A nucleolar isoform of the Fbw7 ubiquitin ligase regulates c-Myc and cell size. Curr Biol. 2004;14:1852-7 pubmed
    The human tumor suppressor Fbw7/hCdc4 functions as a phosphoepitope-specific substrate recognition component of SCF ubiquitin ligases that catalyzes the ubiquitination of cyclin E , Notch , c-Jun and c-Myc ...
  57. Popov N, Wanzel M, Madiredjo M, Zhang D, Beijersbergen R, Bernards R, et al. The ubiquitin-specific protease USP28 is required for MYC stability. Nat Cell Biol. 2007;9:765-74 pubmed
    ..High expression levels of USP28 are found in colon and breast carcinomas, and stabilization of MYC by USP28 is essential for tumour-cell proliferation. ..
  58. 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. ..
  59. Welcker M, Singer J, Loeb K, Grim J, Bloecher A, Gurien West M, et al. Multisite phosphorylation by Cdk2 and GSK3 controls cyclin E degradation. Mol Cell. 2003;12:381-92 pubmed
    ..abundance: phosphorylation of cyclin E on T380 by its associated CDK allows binding to the receptor subunit, Fbw7, of the SCFFbw7 ubiquitin ligase...
  60. Finkin S, Aylon Y, Anzi S, Oren M, Shaulian E. Fbw7 regulates the activity of endoreduplication mediators and the p53 pathway to prevent drug-induced polyploidy. Oncogene. 2008;27:4411-21 pubmed publisher
    b>Fbw7 is a tumor suppressor that is mutated in numerous cancers. It encodes an E3 ubiquitin ligase, whose ability to decrease the levels of pivotal regulators of cell growth and proliferation underlies its tumor suppressor function...
  61. Miyaki M, Yamaguchi T, Iijima T, Takahashi K, Matsumoto H, Mori T. Somatic mutations of the CDC4 (FBXW7) gene in hereditary colorectal tumors. Oncology. 2009;76:430-4 pubmed publisher
    Cdc4 (Fbxw7) is a potential tumor suppressor that regulates ubiquitination and proteolysis of multiple targets such as cyclin E, c-Myc, c-Jun and Notch...
  62. Popov N, Herold S, Llamazares M, Schülein C, Eilers M. Fbw7 and Usp28 regulate myc protein stability in response to DNA damage. Cell Cycle. 2007;6:2327-31 pubmed
    ..We show here that this decline is in part due to proteasomal degradation and that it is mediated by the Fbw7 ubiquitin ligase...
  63. Mansour M, Sulis M, Duke V, Foroni L, Jenkinson S, Koo K, et al. Prognostic implications of NOTCH1 and FBXW7 mutations in adults with T-cell acute lymphoblastic leukemia treated on the MRC UKALLXII/ECOG E2993 protocol. J Clin Oncol. 2009;27:4352-6 pubmed publisher
    Notch pathway activation by mutations in either NOTCH1 and/or FBXW7 is one of the most common molecular events in T-cell acute lymphoblastic leukemia (T-ALL) and, in pediatric disease, predicts for favorable outcome...
  64. Xu Y, Sengupta T, Kukreja L, Minella A. MicroRNA-223 regulates cyclin E activity by modulating expression of F-box and WD-40 domain protein 7. J Biol Chem. 2010;285:34439-46 pubmed publisher
    ..Fbw7 is a bona fide tumor suppressor, and loss-of-function mutations in FBXW7 have been identified in diverse human tumors...