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<!-- The PBB_Controls template provides controls for Protein Box Bot, please see Template:PBB_Controls for details. -->
{{Infobox_gene}}
{{PBB_Controls
'''F-box/WD repeat-containing protein 7''' is a [[protein]] that in humans is encoded by the ''FBXW7'' [[gene]].<ref name="pmid10531037">{{cite journal | vauthors = Winston JT, Koepp DM, Zhu C, Elledge SJ, Harper JW | title = A family of mammalian F-box proteins | journal = Curr Biol | volume = 9 | issue = 20 | pages = 1180–2 | date = Dec 1999 | pmid = 10531037 | pmc =  | doi = 10.1016/S0960-9822(00)80021-4 }}</ref><ref name="pmid11425854">{{cite journal | vauthors = Gupta-Rossi N, Le Bail O, Gonen H, Brou C, Logeat F, Six E, Ciechanover A, Israël A | title = Functional interaction between SEL-10, an F-box protein, and the nuclear form of activated Notch1 receptor | journal = J Biol Chem | volume = 276 | issue = 37 | pages = 34371–8 | date = Sep 2001 | pmid = 11425854 | pmc = | doi = 10.1074/jbc.M101343200 }}</ref><ref name="entrez">{{cite web | title = Entrez Gene: FBXW7 F-box and WD repeat domain containing 7| url = https://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=55294| accessdate = }}</ref>
| update_page = yes
| require_manual_inspection = no
| update_protein_box = yes
| update_summary = yes
| update_citations = yes
}}


<!-- The GNF_Protein_box is automatically maintained by Protein Box Bot.  See Template:PBB_Controls to Stop updates. -->
== Function ==
{{GNF_Protein_box
| image = PBB_Protein_FBXW7_image.jpg
| image_source = [[Protein_Data_Bank|PDB]] rendering based on 2ovp.
| PDB = {{PDB2|2ovp}}, {{PDB2|2ovq}}, {{PDB2|2ovr}}
| Name = F-box and WD repeat domain containing 7
| HGNCid = 16712
| Symbol = FBXW7
| AltSymbols =; AGO; CDC4; DKFZp686F23254; FBW7; FBX30; FBXW6; SEL-10; SEL10
| OMIM = 606278
| ECnumber = 
| Homologene = 69520
| MGIid = 1354695
| GeneAtlas_image1 = PBB_GE_FBXW7_218751_s_at_tn.png
| Function = {{GNF_GO|id=GO:0003700 |text = transcription factor activity}} {{GNF_GO|id=GO:0005515 |text = protein binding}}
| Component = {{GNF_GO|id=GO:0005634 |text = nucleus}} {{GNF_GO|id=GO:0005783 |text = endoplasmic reticulum}} {{GNF_GO|id=GO:0005794 |text = Golgi apparatus}}
| Process = {{GNF_GO|id=GO:0007219 |text = Notch signaling pathway}} {{GNF_GO|id=GO:0016567 |text = protein ubiquitination}}
| Orthologs = {{GNF_Ortholog_box
    | Hs_EntrezGene = 55294
    | Hs_Ensembl = ENSG00000109670
    | Hs_RefseqProtein = NP_001013433
    | Hs_RefseqmRNA = NM_001013415
    | Hs_GenLoc_db = 
    | Hs_GenLoc_chr = 4
    | Hs_GenLoc_start = 153461860
    | Hs_GenLoc_end = 153675622
    | Hs_Uniprot = Q969H0
    | Mm_EntrezGene = 50754
    | Mm_Ensembl = ENSMUSG00000028086
    | Mm_RefseqmRNA = NM_080428
    | Mm_RefseqProtein = NP_536353
    | Mm_GenLoc_db = 
    | Mm_GenLoc_chr = 3
    | Mm_GenLoc_start = 85038138
    | Mm_GenLoc_end = 85063572
    | Mm_Uniprot = Q8VBV4
  }}
}}
'''F-box and WD repeat domain containing 7''', also known as '''FBXW7''', is a human [[gene]].<ref name="entrez">{{cite web | title = Entrez Gene: FBXW7 F-box and WD repeat domain containing 7| url = http://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=55294| accessdate = }}</ref>


<!-- The PBB_Summary template is automatically maintained by Protein Box Bot.  See Template:PBB_Controls to Stop updates. -->
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 ligase|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. Other well established pro-proliferative targets of FBXW7 are c-Myc and Notch1. Mono-allelic mutations in this gene are detected in sporadic cancers [e.g., cholangiocarcinoma (35%), T-ALL (31%), endometrial carcinoma (16%), colorectal carcinoma (16%), bladder cancer (10%), gastric carcinoma (6%), lung squamous cell carcinoma (5%), etc.]. These findings implicate the gene's potential role in the pathogenesis of human cancers. Despite being commonly acknowledged as a haploinsufficient tumor suppressor, mutations are not found in some cancers, such as acute myeloid leukemia and multiple myeloma. One possibility is that FBXW7 substrate stabilization is detrimental in these neoplasms. For example, the FBXW7 substrate C/EBPα suppresses AML<ref name="pmid20534483">{{cite journal | vauthors = Bengoechea-Alonso MT, Ericsson J | title = The ubiquitin ligase Fbxw7 controls adipocyte differentiation by targeting C/EBPalpha for degradation | journal = Proceedings of the National Academy of Sciences of the United States of America | volume = 107 | issue = 26 | pages = 11817–22 | date = June 2010 | pmid = 20534483 | pmc = 2900639 | doi = 10.1073/pnas.0913367107 }}</ref> and multiple myelomas require constitutive NF-κB signaling; therefore, disruption of FBXW7-mediated ubiquitylation of IκBd in these tumors results in cell death.<ref name="pmid22388891">{{cite journal | vauthors = Busino L, Millman SE, Scotto L, Kyratsous CA, Basrur V, O'Connor O, Hoffmann A, Elenitoba-Johnson KS, Pagano M | title = Fbxw7α- and GSK3-mediated degradation of p100 is a pro-survival mechanism in multiple myeloma | journal = Nature Cell Biology | volume = 14 | issue = 4 | pages = 375–85 | date = March 2012 | pmid = 22388891 | pmc = 3339029 | doi = }}</ref><ref name="pmid23211527">{{cite journal | vauthors = Busino L, Millman SE, Pagano M | title = SCF-mediated degradation of p100 (NF-κB2): mechanisms and relevance in multiple myeloma | journal = Science Signaling | volume = 5 | issue = 253 | pages = pt14 | date = December 2012 | pmid = 23211527 | pmc = 3871187 | doi = 10.1126/scisignal.2003408 }}</ref>
{{PBB_Summary
| section_title =
| summary_text = 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.<ref name="entrez">{{cite web | title = Entrez Gene: FBXW7 F-box and WD repeat domain containing 7| url = http://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=55294| accessdate = }}</ref>
}}


==References==
Three transcript variants encoding three different isoforms have been found for this gene.<ref name="entrez" />
{{reflist|2}}
 
==Further reading==
== Interactions ==
 
FBXW7 has been shown to [[Protein-protein interaction|interact]] with:
* [[MYB (gene)|MYB]],<ref name = pmid18765672>{{cite journal | vauthors = Kanei-Ishii C, Nomura T, Takagi T, Watanabe N, Nakayama KI, Ishii S | title = Fbxw7 acts as an E3 ubiquitin ligase that targets c-Myb for nemo-like kinase (NLK)-induced degradation | journal = J. Biol. Chem. | volume = 283 | issue = 45 | pages = 30540–8 | date = Nov 2008 | pmid = 18765672 | pmc = 2662147 | doi = 10.1074/jbc.M804340200 }}</ref>
* [[PPARGC1A]],<ref name = pmid18198341>{{cite journal | vauthors = Olson BL, Hock MB, Ekholm-Reed S, Wohlschlegel JA, Dev KK, Kralli A, Reed SI | title = SCFCdc4 acts antagonistically to the PGC-1alpha transcriptional coactivator by targeting it for ubiquitin-mediated proteolysis | journal = Genes Dev. | volume = 22 | issue = 2 | pages = 252–64 | date = Jan 2008 | pmid = 18198341 | pmc = 2192758 | doi = 10.1101/gad.1624208 }}</ref>
* [[Parkin (ligase)]],<ref name = pmid12628165>{{cite journal | vauthors = Staropoli JF, McDermott C, Martinat C, Schulman B, Demireva E, Abeliovich A | title = Parkin is a component of an SCF-like ubiquitin ligase complex and protects postmitotic neurons from kainate excitotoxicity | journal = Neuron | volume = 37 | issue = 5 | pages = 735–49 | date = Mar 2003 | pmid = 12628165 | doi =  10.1016/s0896-6273(03)00084-9}}</ref>  and
* [[SKP1A]].<ref name = pmid12628165/><ref name = pmid11585921>{{cite journal | vauthors = Wu G, Lyapina S, Das I, Li J, Gurney M, Pauley A, Chui I, Deshaies RJ, Kitajewski J | title = SEL-10 is an inhibitor of notch signaling that targets notch for ubiquitin-mediated protein degradation | journal = Mol. Cell. Biol. | volume = 21 | issue = 21 | pages = 7403–15 | date = Nov 2001 | pmid = 11585921 | pmc = 99913 | doi = 10.1128/MCB.21.21.7403-7415.2001 }}</ref>
 
== References ==
{{reflist}}
 
== Further reading ==
{{refbegin | 2}}
{{refbegin | 2}}
{{PBB_Further_reading
* {{cite journal | vauthors = Robertson NG, Khetarpal U, Gutiérrez-Espeleta GA, Bieber FR, Morton CC | title = Isolation of novel and known genes from a human fetal cochlear cDNA library using subtractive hybridization and differential screening | journal = Genomics | volume = 23 | issue = 1 | pages = 42–50 | year = 1995 | pmid = 7829101 | doi = 10.1006/geno.1994.1457 }}
| citations =
* {{cite journal | vauthors = Maruyama K, Sugano S | title = Oligo-capping: a simple method to replace the cap structure of eukaryotic mRNAs with oligoribonucleotides | journal = Gene | volume = 138 | issue = 1–2 | pages = 171–4 | year = 1994 | pmid = 8125298 | doi = 10.1016/0378-1119(94)90802-8 }}
*{{cite journal | author=Robertson NG, Khetarpal U, Gutiérrez-Espeleta GA, ''et al.'' |title=Isolation of novel and known genes from a human fetal cochlear cDNA library using subtractive hybridization and differential screening. |journal=Genomics |volume=23 |issue= 1 |pages= 42-50 |year= 1995 |pmid= 7829101 |doi= 10.1006/geno.1994.1457 }}
* {{cite journal | vauthors = Suzuki Y, Yoshitomo-Nakagawa K, Maruyama K, Suyama A, Sugano S | title = Construction and characterization of a full length-enriched and a 5'-end-enriched cDNA library | journal = Gene | volume = 200 | issue = 1–2 | pages = 149–56 | year = 1997 | pmid = 9373149 | doi = 10.1016/S0378-1119(97)00411-3 }}
*{{cite journal | author=Maruyama K, Sugano S |title=Oligo-capping: a simple method to replace the cap structure of eukaryotic mRNAs with oligoribonucleotides. |journal=Gene |volume=138 |issue= 1-2 |pages= 171-4 |year= 1994 |pmid= 8125298 |doi= }}
* {{cite journal | vauthors = Oberg C, Li J, Pauley A, Wolf E, Gurney M, Lendahl U | title = The Notch intracellular domain is ubiquitinated and negatively regulated by the mammalian Sel-10 homolog | journal = J. Biol. Chem. | volume = 276 | issue = 38 | pages = 35847–53 | year = 2001 | pmid = 11461910 | doi = 10.1074/jbc.M103992200 }}
*{{cite journal | author=Suzuki Y, Yoshitomo-Nakagawa K, Maruyama K, ''et al.'' |title=Construction and characterization of a full length-enriched and a 5'-end-enriched cDNA library. |journal=Gene |volume=200 |issue= 1-2 |pages= 149-56 |year= 1997 |pmid= 9373149 |doi=  }}
* {{cite journal | vauthors = Koepp DM, Schaefer LK, Ye X, Keyomarsi K, Chu C, Harper JW, Elledge SJ | title = Phosphorylation-dependent ubiquitination of cyclin E by the SCFFbw7 ubiquitin ligase | journal = Science | volume = 294 | issue = 5540 | pages = 173–7 | year = 2001 | pmid = 11533444 | doi = 10.1126/science.1065203 }}
*{{cite journal  | author=Winston JT, Koepp DM, Zhu C, ''et al.'' |title=A family of mammalian F-box proteins. |journal=Curr. Biol. |volume=9 |issue= 20 |pages= 1180-2 |year= 1999 |pmid= 10531037 |doi= 10.1016/S0960-9822(00)80021-4 }}
* {{cite journal | vauthors = Moberg KH, Bell DW, Wahrer DC, Haber DA, Hariharan IK | title = Archipelago regulates Cyclin E levels in Drosophila and is mutated in human cancer cell lines | journal = Nature | volume = 413 | issue = 6853 | pages = 311–6 | year = 2001 | pmid = 11565033 | doi = 10.1038/35095068 }}
*{{cite journal | author=Gupta-Rossi N, Le Bail O, Gonen H, ''et al.'' |title=Functional interaction between SEL-10, an F-box protein, and the nuclear form of activated Notch1 receptor. |journal=J. Biol. Chem. |volume=276 |issue= 37 |pages= 34371-8 |year= 2001 |pmid= 11425854 |doi= 10.1074/jbc.M101343200 }}
* {{cite journal | vauthors = Strohmaier H, Spruck CH, Kaiser P, Won KA, Sangfelt O, Reed SI | title = Human F-box protein hCdc4 targets cyclin E for proteolysis and is mutated in a breast cancer cell line | journal = Nature | volume = 413 | issue = 6853 | pages = 316–22 | year = 2001 | pmid = 11565034 | doi = 10.1038/35095076 }}
*{{cite journal  | author=Oberg C, Li J, Pauley A, ''et al.'' |title=The Notch intracellular domain is ubiquitinated and negatively regulated by the mammalian Sel-10 homolog. |journal=J. Biol. Chem. |volume=276 |issue= 38 |pages= 35847-53 |year= 2001 |pmid= 11461910 |doi= 10.1074/jbc.M103992200 }}
* {{cite journal | vauthors = Wu G, Lyapina S, Das I, Li J, Gurney M, Pauley A, Chui I, Deshaies RJ, Kitajewski J | title = SEL-10 Is an Inhibitor of Notch Signaling That Targets Notch for Ubiquitin-Mediated Protein Degradation | journal = Mol. Cell. Biol. | volume = 21 | issue = 21 | pages = 7403–15 | year = 2001 | pmid = 11585921 | pmc = 99913 | doi = 10.1128/MCB.21.21.7403-7415.2001 }}
*{{cite journal | author=Koepp DM, Schaefer LK, Ye X, ''et al.'' |title=Phosphorylation-dependent ubiquitination of cyclin E by the SCFFbw7 ubiquitin ligase. |journal=Science |volume=294 |issue= 5540 |pages= 173-7 |year= 2001 |pmid= 11533444 |doi= 10.1126/science.1065203 }}
* {{cite journal | vauthors = Spruck CH, Strohmaier H, Sangfelt O, Müller HM, Hubalek M, Müller-Holzner E, Marth C, Widschwendter M, Reed SI | title = hCDC4 gene mutations in endometrial cancer | journal = Cancer Res. | volume = 62 | issue = 16 | pages = 4535–9 | year = 2002 | pmid = 12183400 | doi =  }}
*{{cite journal | author=Moberg KH, Bell DW, Wahrer DC, ''et al.'' |title=Archipelago regulates Cyclin E levels in Drosophila and is mutated in human cancer cell lines. |journal=Nature |volume=413 |issue= 6853 |pages= 311-6 |year= 2001 |pmid= 11565033 |doi= 10.1038/35095068 }}
* {{cite journal | vauthors = Li J, Pauley AM, Myers RL, Shuang R, Brashler JR, Yan R, Buhl AE, Ruble C, Gurney ME | title = SEL-10 interacts with presenilin 1, facilitates its ubiquitination, and alters A-beta peptide production | journal = J. Neurochem. | volume = 82 | issue = 6 | pages = 1540–8 | year = 2002 | pmid = 12354302 | doi = 10.1046/j.1471-4159.2002.01105.x }}
*{{cite journal | author=Strohmaier H, Spruck CH, Kaiser P, ''et al.'' |title=Human F-box protein hCdc4 targets cyclin E for proteolysis and is mutated in a breast cancer cell line. |journal=Nature |volume=413 |issue= 6853 |pages= 316-22 |year= 2001 |pmid= 11565034 |doi= 10.1038/35095076 }}
* {{cite journal | vauthors = Staropoli JF, McDermott C, Martinat C, Schulman B, Demireva E, Abeliovich A | title = Parkin is a component of an SCF-like ubiquitin ligase complex and protects postmitotic neurons from kainate excitotoxicity | journal = Neuron | volume = 37 | issue = 5 | pages = 735–49 | year = 2003 | pmid = 12628165 | doi = 10.1016/S0896-6273(03)00084-9 }}
*{{cite journal | author=Wu G, Lyapina S, Das I, ''et al.'' |title=SEL-10 is an inhibitor of notch signaling that targets notch for ubiquitin-mediated protein degradation. |journal=Mol. Cell. Biol. |volume=21 |issue= 21 |pages= 7403-15 |year= 2001 |pmid= 11585921 |doi= 10.1128/MCB.21.21.7403-7415.2001 }}
* {{cite journal | vauthors = Calhoun ES, Jones JB, Ashfaq R, Adsay V, Baker SJ, Valentine V, Hempen PM, Hilgers W, Yeo CJ, Hruban RH, Kern SE | title = BRAF and FBXW7 (CDC4, FBW7, AGO, SEL10) Mutations in Distinct Subsets of Pancreatic Cancer: Potential Therapeutic Targets | journal = Am. J. Pathol. | volume = 163 | issue = 4 | pages = 1255–60 | year = 2003 | pmid = 14507635 | pmc = 1868306 | doi = 10.1016/S0002-9440(10)63485-2 }}
*{{cite journal | author=Spruck CH, Strohmaier H, Sangfelt O, ''et al.'' |title=hCDC4 gene mutations in endometrial cancer. |journal=Cancer Res. |volume=62 |issue= 16 |pages= 4535-9 |year= 2002 |pmid= 12183400 |doi=  }}
* {{cite journal | vauthors = Welcker M, Singer J, Loeb KR, Grim J, Bloecher A, Gurien-West M, Clurman BE, Roberts JM | title = Multisite phosphorylation by Cdk2 and GSK3 controls cyclin E degradation | journal = Mol. Cell | volume = 12 | issue = 2 | pages = 381–92 | year = 2003 | pmid = 14536078 | doi = 10.1016/S1097-2765(03)00287-9 }}
*{{cite journal | author=Li J, Pauley AM, Myers RL, ''et al.'' |title=SEL-10 interacts with presenilin 1, facilitates its ubiquitination, and alters A-beta peptide production. |journal=J. Neurochem. |volume=82 |issue= 6 |pages= 1540-8 |year= 2002 |pmid= 12354302 |doi= }}
* {{cite journal | vauthors = Busino L, Donzelli M, Chiesa M, Guardavaccaro D, Ganoth D, Dorrello NV, Hershko A, Pagano M, Draetta GF | title = Degradation of Cdc25A by beta-TrCP during S phase and in response to DNA damage | journal = Nature | volume = 426 | issue = 6962 | pages = 87–91 | year = 2003 | pmid = 14603323 | doi = 10.1038/nature02082 }}
*{{cite journal  | author=Strausberg RL, Feingold EA, Grouse LH, ''et al.'' |title=Generation and initial analysis of more than 15,000 full-length human and mouse cDNA sequences. |journal=Proc. Natl. Acad. Sci. U.S.A. |volume=99 |issue= 26 |pages= 16899-903 |year= 2003 |pmid= 12477932 |doi= 10.1073/pnas.242603899 }}
* {{cite journal | vauthors = Cassia R, Moreno-Bueno G, Rodríguez-Perales S, Hardisson D, Cigudosa JC, Palacios J | title = Cyclin E gene (CCNE) amplification and hCDC4 mutations in endometrial carcinoma | journal = J. Pathol. | volume = 201 | issue = 4 | pages = 589–95 | year = 2004 | pmid = 14648662 | doi = 10.1002/path.1474 }}
*{{cite journal | author=Staropoli JF, McDermott C, Martinat C, ''et al.'' |title=Parkin is a component of an SCF-like ubiquitin ligase complex and protects postmitotic neurons from kainate excitotoxicity. |journal=Neuron |volume=37 |issue= 5 |pages= 735-49 |year= 2003 |pmid= 12628165 |doi= }}
* {{cite journal | vauthors = Nateri AS, Riera-Sans L, Da Costa C, Behrens A | title = The ubiquitin ligase SCFFbw7 antagonizes apoptotic JNK signaling | journal = Science | volume = 303 | issue = 5662 | pages = 1374–8 | year = 2004 | pmid = 14739463 | doi = 10.1126/science.1092880 }}
*{{cite journal | author=Calhoun ES, Jones JB, Ashfaq R, ''et al.'' |title=BRAF and FBXW7 (CDC4, FBW7, AGO, SEL10) mutations in distinct subsets of pancreatic cancer: potential therapeutic targets. |journal=Am. J. Pathol. |volume=163 |issue= 4 |pages= 1255-60 |year= 2003 |pmid= 14507635 |doi= }}
*{{cite journal | author=Welcker M, Singer J, Loeb KR, ''et al.'' |title=Multisite phosphorylation by Cdk2 and GSK3 controls cyclin E degradation. |journal=Mol. Cell |volume=12 |issue= 2 |pages= 381-92 |year= 2003 |pmid= 14536078 |doi= }}
*{{cite journal | author=Busino L, Donzelli M, Chiesa M, ''et al.'' |title=Degradation of Cdc25A by beta-TrCP during S phase and in response to DNA damage. |journal=Nature |volume=426 |issue= 6962 |pages= 87-91 |year= 2003 |pmid= 14603323 |doi= 10.1038/nature02082 }}
*{{cite journal | author=Cassia R, Moreno-Bueno G, Rodríguez-Perales S, ''et al.'' |title=Cyclin E gene (CCNE) amplification and hCDC4 mutations in endometrial carcinoma. |journal=J. Pathol. |volume=201 |issue= 4 |pages= 589-95 |year= 2004 |pmid= 14648662 |doi= 10.1002/path.1474 }}
*{{cite journal | author=Ota T, Suzuki Y, Nishikawa T, ''et al.'' |title=Complete sequencing and characterization of 21,243 full-length human cDNAs. |journal=Nat. Genet. |volume=36 |issue= 1 |pages= 40-5 |year= 2004 |pmid= 14702039 |doi= 10.1038/ng1285 }}
*{{cite journal  | author=Nateri AS, Riera-Sans L, Da Costa C, Behrens A |title=The ubiquitin ligase SCFFbw7 antagonizes apoptotic JNK signaling. |journal=Science |volume=303 |issue= 5662 |pages= 1374-8 |year= 2004 |pmid= 14739463 |doi= 10.1126/science.1092880 }}
}}
{{refend}}
{{refend}}


{{protein-stub}}
{{PDB Gallery|geneid=55294}}
{{WikiDoc Sources}}
 
 
{{gene-4-stub}}

Latest revision as of 12:03, 10 January 2019

VALUE_ERROR (nil)
Identifiers
Aliases
External IDsGeneCards: [1]
Orthologs
SpeciesHumanMouse
Entrez

n/a

n/a

Ensembl

n/a

n/a

UniProt

n/a

n/a

RefSeq (mRNA)

n/a

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RefSeq (protein)

n/a

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Location (UCSC)n/an/a
PubMed searchn/an/a
Wikidata
View/Edit Human

F-box/WD repeat-containing protein 7 is a protein that in humans is encoded by the FBXW7 gene.[1][2][3]

Function

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. Other well established pro-proliferative targets of FBXW7 are c-Myc and Notch1. Mono-allelic mutations in this gene are detected in sporadic cancers [e.g., cholangiocarcinoma (35%), T-ALL (31%), endometrial carcinoma (16%), colorectal carcinoma (16%), bladder cancer (10%), gastric carcinoma (6%), lung squamous cell carcinoma (5%), etc.]. These findings implicate the gene's potential role in the pathogenesis of human cancers. Despite being commonly acknowledged as a haploinsufficient tumor suppressor, mutations are not found in some cancers, such as acute myeloid leukemia and multiple myeloma. One possibility is that FBXW7 substrate stabilization is detrimental in these neoplasms. For example, the FBXW7 substrate C/EBPα suppresses AML[4] and multiple myelomas require constitutive NF-κB signaling; therefore, disruption of FBXW7-mediated ubiquitylation of IκBd in these tumors results in cell death.[5][6]

Three transcript variants encoding three different isoforms have been found for this gene.[3]

Interactions

FBXW7 has been shown to interact with:

References

  1. ↑ 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.
  2. ↑ Gupta-Rossi N, Le Bail O, Gonen H, Brou C, Logeat F, Six E, Ciechanover A, Israël 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.
  3. ↑ 3.0 3.1 "Entrez Gene: FBXW7 F-box and WD repeat domain containing 7".
  4. ↑ Bengoechea-Alonso MT, Ericsson J (June 2010). "The ubiquitin ligase Fbxw7 controls adipocyte differentiation by targeting C/EBPalpha for degradation". Proceedings of the National Academy of Sciences of the United States of America. 107 (26): 11817–22. doi:10.1073/pnas.0913367107. PMC 2900639. PMID 20534483.
  5. ↑ Busino L, Millman SE, Scotto L, Kyratsous CA, Basrur V, O'Connor O, Hoffmann A, Elenitoba-Johnson KS, Pagano M (March 2012). "Fbxw7α- and GSK3-mediated degradation of p100 is a pro-survival mechanism in multiple myeloma". Nature Cell Biology. 14 (4): 375–85. PMC 3339029. PMID 22388891.
  6. ↑ Busino L, Millman SE, Pagano M (December 2012). "SCF-mediated degradation of p100 (NF-κB2): mechanisms and relevance in multiple myeloma". Science Signaling. 5 (253): pt14. doi:10.1126/scisignal.2003408. PMC 3871187. PMID 23211527.
  7. ↑ Kanei-Ishii C, Nomura T, Takagi T, Watanabe N, Nakayama KI, Ishii S (Nov 2008). "Fbxw7 acts as an E3 ubiquitin ligase that targets c-Myb for nemo-like kinase (NLK)-induced degradation". J. Biol. Chem. 283 (45): 30540–8. doi:10.1074/jbc.M804340200. PMC 2662147. PMID 18765672.
  8. ↑ Olson BL, Hock MB, Ekholm-Reed S, Wohlschlegel JA, Dev KK, Kralli A, Reed SI (Jan 2008). "SCFCdc4 acts antagonistically to the PGC-1alpha transcriptional coactivator by targeting it for ubiquitin-mediated proteolysis". Genes Dev. 22 (2): 252–64. doi:10.1101/gad.1624208. PMC 2192758. PMID 18198341.
  9. ↑ 9.0 9.1 Staropoli JF, McDermott C, Martinat C, Schulman B, Demireva E, Abeliovich A (Mar 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.
  10. ↑ Wu G, Lyapina S, Das I, Li J, Gurney M, Pauley A, Chui I, Deshaies RJ, Kitajewski J (Nov 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.

Further reading


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