FBXW7
F-box/WD repeat-containing protein 7 is a protein that in humans is encoded by the FBXW7 gene.[1][2][3]
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. Three transcript variants encoding three different isoforms have been found for this gene.[3]
Interactions
FBXW7 has been shown to interact with PPARGC1A,[4] Parkin (ligase),[5] MYB[6] and SKP1A.[5][7]
References
- ^ Winston JT, Koepp DM, Zhu C, Elledge SJ, Harper JW (Dec 1999). "A family of mammalian F-box proteins". Curr Biol 9 (20): 1180–2. doi:10.1016/S0960-9822(00)80021-4. PMID 10531037.
- ^ Gupta-Rossi N, Le Bail O, Gonen H, Brou C, Logeat F, Six E, Ciechanover A, Israel A (Sep 2001). "Functional interaction between SEL-10, an F-box protein, and the nuclear form of activated Notch1 receptor". J Biol Chem 276 (37): 34371–8. doi:10.1074/jbc.M101343200. PMID 11425854.
- ^ a b "Entrez Gene: FBXW7 F-box and WD repeat domain containing 7". http://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=55294.
- ^ Olson, Brian L; Hock M Benjamin, Ekholm-Reed Susanna, Wohlschlegel James A, Dev Kumlesh K, Kralli Anastasia, Reed Steven I (Jan. 2008). "SCFCdc4 acts antagonistically to the PGC-1α transcriptional coactivator by targeting it for ubiquitin-mediated proteolysis". Genes Dev. (United States) 22 (2): 252–64. doi:10.1101/gad.1624208. ISSN 0890-9369. PMC 2192758. PMID 18198341. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=2192758.
- ^ a b Staropoli, John F; McDermott Caroline, Martinat Cécile, Schulman Brenda, Demireva Elena, Abeliovich Asa (Mar. 2003). "Parkin is a component of an SCF-like ubiquitin ligase complex and protects postmitotic neurons from kainate excitotoxicity". Neuron (United States) 37 (5): 735–49. doi:10.1016/S0896-6273(03)00084-9. ISSN 0896-6273. PMID 12628165.
- ^ Kanei-Ishii, Chie; Nomura Teruaki, Takagi Tsuyoshi, Watanabe Nobumoto, Nakayama Keiichi I, Ishii Shunsuke (Nov. 2008). "Fbxw7 Acts as an E3 Ubiquitin Ligase That Targets c-Myb for Nemo-like Kinase (NLK)-induced Degradation". J. Biol. Chem. (United States) 283 (45): 30540–8. doi:10.1074/jbc.M804340200. ISSN 0021-9258. PMC 2662147. PMID 18765672. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=2662147.
- ^ Wu, G; Lyapina S, Das I, Li J, Gurney M, Pauley A, Chui I, Deshaies R J, Kitajewski J (Nov. 2001). "SEL-10 Is an Inhibitor of Notch Signaling That Targets Notch for Ubiquitin-Mediated Protein Degradation". Mol. Cell. Biol. (United States) 21 (21): 7403–15. doi:10.1128/MCB.21.21.7403-7415.2001. ISSN 0270-7306. PMC 99913. PMID 11585921. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=99913.
Further reading
- Robertson NG, Khetarpal U, Gutiérrez-Espeleta GA, et al. (1995). "Isolation of novel and known genes from a human fetal cochlear cDNA library using subtractive hybridization and differential screening". Genomics 23 (1): 42–50. doi:10.1006/geno.1994.1457. PMID 7829101.
- Maruyama K, Sugano S (1994). "Oligo-capping: a simple method to replace the cap structure of eukaryotic mRNAs with oligoribonucleotides". Gene 138 (1–2): 171–4. doi:10.1016/0378-1119(94)90802-8. PMID 8125298.
- Suzuki Y, Yoshitomo-Nakagawa K, Maruyama K, et al. (1997). "Construction and characterization of a full length-enriched and a 5'-end-enriched cDNA library". Gene 200 (1–2): 149–56. doi:10.1016/S0378-1119(97)00411-3. PMID 9373149.
- Oberg C, Li J, Pauley A, et al. (2001). "The Notch intracellular domain is ubiquitinated and negatively regulated by the mammalian Sel-10 homolog". J. Biol. Chem. 276 (38): 35847–53. doi:10.1074/jbc.M103992200. PMID 11461910.
- Koepp DM, Schaefer LK, Ye X, et al. (2001). "Phosphorylation-dependent ubiquitination of cyclin E by the SCFFbw7 ubiquitin ligase". Science 294 (5540): 173–7. doi:10.1126/science.1065203. PMID 11533444.
- Moberg KH, Bell DW, Wahrer DC, et al. (2001). "Archipelago regulates Cyclin E levels in Drosophila and is mutated in human cancer cell lines". Nature 413 (6853): 311–6. doi:10.1038/35095068. PMID 11565033.
- Strohmaier H, Spruck CH, Kaiser P, et al. (2001). "Human F-box protein hCdc4 targets cyclin E for proteolysis and is mutated in a breast cancer cell line". Nature 413 (6853): 316–22. doi:10.1038/35095076. PMID 11565034.
- Wu G, Lyapina S, Das I, et al. (2001). "SEL-10 Is an Inhibitor of Notch Signaling That Targets Notch for Ubiquitin-Mediated Protein Degradation". Mol. Cell. Biol. 21 (21): 7403–15. doi:10.1128/MCB.21.21.7403-7415.2001. PMC 99913. PMID 11585921. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=99913.
- Spruck CH, Strohmaier H, Sangfelt O, et al. (2002). "hCDC4 gene mutations in endometrial cancer". Cancer Res. 62 (16): 4535–9. PMID 12183400.
- Li J, Pauley AM, Myers RL, et al. (2002). "SEL-10 interacts with presenilin 1, facilitates its ubiquitination, and alters A-beta peptide production". J. Neurochem. 82 (6): 1540–8. doi:10.1046/j.1471-4159.2002.01105.x. PMID 12354302.
- Strausberg RL, Feingold EA, Grouse LH, et al. (2003). "Generation and initial analysis of more than 15,000 full-length human and mouse cDNA sequences". Proc. Natl. Acad. Sci. U.S.A. 99 (26): 16899–903. doi:10.1073/pnas.242603899. PMC 139241. PMID 12477932. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=139241.
- Staropoli JF, McDermott C, Martinat C, et al. (2003). "Parkin is a component of an SCF-like ubiquitin ligase complex and protects postmitotic neurons from kainate excitotoxicity". Neuron 37 (5): 735–49. doi:10.1016/S0896-6273(03)00084-9. PMID 12628165.
- Calhoun ES, Jones JB, Ashfaq R, et al. (2003). "BRAF and FBXW7 (CDC4, FBW7, AGO, SEL10) Mutations in Distinct Subsets of Pancreatic Cancer: Potential Therapeutic Targets". Am. J. Pathol. 163 (4): 1255–60. doi:10.1016/S0002-9440(10)63485-2. PMC 1868306. PMID 14507635. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=1868306.
- Welcker M, Singer J, Loeb KR, et al. (2003). "Multisite phosphorylation by Cdk2 and GSK3 controls cyclin E degradation". Mol. Cell 12 (2): 381–92. doi:10.1016/S1097-2765(03)00287-9. PMID 14536078.
- Busino L, Donzelli M, Chiesa M, et al. (2003). "Degradation of Cdc25A by beta-TrCP during S phase and in response to DNA damage". Nature 426 (6962): 87–91. doi:10.1038/nature02082. PMID 14603323.
- Cassia R, Moreno-Bueno G, Rodríguez-Perales S, et al. (2004). "Cyclin E gene (CCNE) amplification and hCDC4 mutations in endometrial carcinoma". J. Pathol. 201 (4): 589–95. doi:10.1002/path.1474. PMID 14648662.
- Ota T, Suzuki Y, Nishikawa T, et al. (2004). "Complete sequencing and characterization of 21,243 full-length human cDNAs". Nat. Genet. 36 (1): 40–5. doi:10.1038/ng1285. PMID 14702039.
- Nateri AS, Riera-Sans L, Da Costa C, Behrens A (2004). "The ubiquitin ligase SCFFbw7 antagonizes apoptotic JNK signaling". Science 303 (5662): 1374–8. doi:10.1126/science.1092880. PMID 14739463.
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PDB gallery
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2ovp: Structure of the Skp1-Fbw7 complex
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2ovq: Structure of the Skp1-Fbw7-CyclinEdegC complex
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2ovr: Structure of the Skp1-Fbw7-CyclinEdegN complex
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