FBXO5 explained

F-box only protein 5 is a protein that in humans is encoded by the FBXO5 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 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. This protein is similar to xenopus early mitotic inhibitor-1 (Emi1), which is a mitotic regulator that interacts with Cdc20 and inhibits the anaphase promoting complex. Moreover, Emi1 also assembles a CRL1 complex that targets RAD51 for ubiquitin-mediated degradation.^[4]

Disease

Gene and protein expression of FBXO5/Emi1 are increased in many human cancers and increased expression has been shown to cause chromosome instability and cancer.^[5]

Interactions

FBXO5 has been shown to interact with:

• CDC20,
• FZR1,^[6]
• SKP1A.^[7] and
• RAD51.

Further reading

• Gubin AN, Njoroge JM, Bouffard GG, Miller JL . Gene expression in proliferating human erythroid cells . Genomics . 59 . 2 . 168–77 . July 1999 . 10409428 . 10.1006/geno.1999.5855 .
• Chiaur DS, Murthy S, Cenciarelli C, Parks W, Loda M, Inghirami G, Demetrick D, Pagano M . Five human genes encoding F-box proteins: chromosome mapping and analysis in human tumors . Cytogenetics and Cell Genetics . 88 . 3–4 . 255–8 . 2000 . 10828603 . 10.1159/000015532 . 431704 .
• Reimann JD, Freed E, Hsu JY, Kramer ER, Peters JM, Jackson PK . Emi1 is a mitotic regulator that interacts with Cdc20 and inhibits the anaphase promoting complex . Cell . 105 . 5 . 645–55 . June 2001 . 11389834 . 10.1016/S0092-8674(01)00361-0 . 16366514 . free .
• Reimann JD, Jackson PK . Emi1 is required for cytostatic factor arrest in vertebrate eggs . Nature . 416 . 6883 . 850–4 . April 2002 . 11976684 . 10.1038/416850a . 2002Natur.416..850R . 4403891 .
• Hsu JY, Reimann JD, Sørensen CS, Lukas J, Jackson PK . E2F-dependent accumulation of hEmi1 regulates S phase entry by inhibiting APC(Cdh1) . Nature Cell Biology . 4 . 5 . 358–66 . May 2002 . 11988738 . 10.1038/ncb785 . 25403043 .
• Li Z, Hu CY, Mo BQ, Xu JD, Zhao Y . [Effect of beta-carotene on gene expression of breast cancer cells] . AI Zheng = Aizheng = Chinese Journal of Cancer . 22 . 4 . 380–4 . April 2003 . 12703993 .
• Margottin-Goguet F, Hsu JY, Loktev A, Hsieh HM, Reimann JD, Jackson PK . Prophase destruction of Emi1 by the SCF(betaTrCP/Slimb) ubiquitin ligase activates the anaphase promoting complex to allow progression beyond prometaphase . Developmental Cell . 4 . 6 . 813–26 . June 2003 . 12791267 . 10.1016/S1534-5807(03)00153-9 . free .
• Moshe Y, Boulaire J, Pagano M, Hershko A . Role of Polo-like kinase in the degradation of early mitotic inhibitor 1, a regulator of the anaphase promoting complex/cyclosome . Proceedings of the National Academy of Sciences of the United States of America . 101 . 21 . 7937–42 . May 2004 . 15148369 . 419535 . 10.1073/pnas.0402442101 . 2004PNAS..101.7937M . free .
• Hansen DV, Loktev AV, Ban KH, Jackson PK . Plk1 regulates activation of the anaphase promoting complex by phosphorylating and triggering SCFbetaTrCP-dependent destruction of the APC Inhibitor Emi1 . Molecular Biology of the Cell . 15 . 12 . 5623–34 . December 2004 . 15469984 . 532041 . 10.1091/mbc.E04-07-0598 .
• Rual JF, Venkatesan K, Hao T, Hirozane-Kishikawa T, Dricot A, Li N, Berriz GF, Gibbons FD, Dreze M, Ayivi-Guedehoussou N, Klitgord N, Simon C, Boxem M, Milstein S, Rosenberg J, Goldberg DS, Zhang LV, Wong SL, Franklin G, Li S, Albala JS, Lim J, Fraughton C, Llamosas E, Cevik S, Bex C, Lamesch P, Sikorski RS, Vandenhaute J, Zoghbi HY, Smolyar A, Bosak S, Sequerra R, Doucette-Stamm L, Cusick ME, Hill DE, Roth FP, Vidal M . Towards a proteome-scale map of the human protein-protein interaction network . Nature . 437 . 7062 . 1173–8 . October 2005 . 16189514 . 10.1038/nature04209 . 2005Natur.437.1173R . 4427026 .
• Eldridge AG, Loktev AV, Hansen DV, Verschuren EW, Reimann JD, Jackson PK . The evi5 oncogene regulates cyclin accumulation by stabilizing the anaphase-promoting complex inhibitor emi1 . Cell . 124 . 2 . 367–80 . January 2006 . 16439210 . 10.1016/j.cell.2005.10.038 . free .
• Lehman NL, Verschuren EW, Hsu JY, Cherry AM, Jackson PK . Overexpression of the anaphase promoting complex/cyclosome inhibitor Emi1 leads to tetraploidy and genomic instability of p53-deficient cells . Cell Cycle . 5 . 14 . 1569–73 . July 2006 . 16861914 . 10.4161/cc.5.14.2925 . free .
• Miller JJ, Summers MK, Hansen DV, Nachury MV, Lehman NL, Loktev A, Jackson PK . Emi1 stably binds and inhibits the anaphase-promoting complex/cyclosome as a pseudosubstrate inhibitor . Genes & Development . 20 . 17 . 2410–20 . September 2006 . 16921029 . 1560415 . 10.1101/gad.1454006 .
• Marangos P, Verschuren EW, Chen R, Jackson PK, Carroll J . Prophase I arrest and progression to metaphase I in mouse oocytes are controlled by Emi1-dependent regulation of APC(Cdh1) . The Journal of Cell Biology . 176 . 1 . 65–75 . January 2007 . 17190794 . 2063628 . 10.1083/jcb.200607070 .

Notes and References

1. Cenciarelli C, Chiaur DS, Guardavaccaro D, Parks W, Vidal M, Pagano M . Identification of a family of human F-box proteins . Current Biology . 9 . 20 . 1177–9 . October 1999 . 10531035 . 10.1016/S0960-9822(00)80020-2 . 7467493 . free . 1999CBio....9.1177C .
2. Winston JT, Koepp DM, Zhu C, Elledge SJ, Harper JW . A family of mammalian F-box proteins . Current Biology . 9 . 20 . 1180–2 . October 1999 . 10531037 . 10.1016/S0960-9822(00)80021-4 . 14341845 . free . 1999CBio....9.1180W .
3. Web site: Entrez Gene: FBXO5 F-box protein 5.
4. Marzio A, Puccini J, Kwon Y, Maverakis NK, Arbini A, Sung P, Bar-Sagi D, Pagano M . The F-Box Domain-Dependent Activity of EMI1 Regulates PARPi Sensitivity in Triple-Negative Breast Cancers . Molecular Cell . 73 . 2 . 224–237.e6 . January 2019 . 30554948 . 10.1016/j.molcel.2018.11.003 . 6995265 . free .
5. Vaidyanathan S, Cato K, Tang L, Pavey S, Haass NK, Gabrielli BG, Duijf PH . In vivo overexpression of Emi1 promotes chromosome instability and tumorigenesis . Oncogene . 35 . 41 . 5446–5455 . October 2016 . 27065322 . 10.1038/onc.2016.94 . 13540659 . free .
6. Hsu JY, Reimann JD, Sørensen CS, Lukas J, Jackson PK . E2F-dependent accumulation of hEmi1 regulates S phase entry by inhibiting APC(Cdh1) . Nature Cell Biology . 4 . 5 . 358–66 . May 2002 . 11988738 . 10.1038/ncb785 . 25403043 .
7. Cenciarelli C, Chiaur DS, Guardavaccaro D, Parks W, Vidal M, Pagano M . Identification of a family of human F-box proteins . Current Biology . 9 . 20 . 1177–9 . October 1999 . 10531035 . 10.1016/S0960-9822(00)80020-2 . 7467493 . free . 1999CBio....9.1177C .