FBXL3

Summary

Gene Symbol: FBXL3
Description: F-box and leucine rich repeat protein 3
Alias: FBL3, FBL3A, FBXL3A, F-box/LRR-repeat protein 3, F-box and leucine-rich repeat protein 3A, F-box protein Fbl3a, F-box/LRR-repeat protein 3A
Species: human
Products:     FBXL3

Top Publications

  1. Busino L, Bassermann F, Maiolica A, Lee C, Nolan P, Godinho S, et al. SCFFbxl3 controls the oscillation of the circadian clock by directing the degradation of cryptochrome proteins. Science. 2007;316:900-4 pubmed
    ..We found that both Cry1 and Cry2 proteins are ubiquitinated and degraded via the SCF(Fbxl3) ubiquitin ligase complex...
  2. Yoo S, Mohawk J, Siepka S, Shan Y, Huh S, Hong H, et al. Competing E3 ubiquitin ligases govern circadian periodicity by degradation of CRY in nucleus and cytoplasm. Cell. 2013;152:1091-105 pubmed publisher
    ..Past-time, revealed a glycine to glutamate missense mutation in Fbxl21, an F-box protein gene that is a paralog of Fbxl3 that targets the CRY proteins for degradation...
  3. Hirano A, Yumimoto K, Tsunematsu R, Matsumoto M, Oyama M, Kozuka Hata H, et al. FBXL21 regulates oscillation of the circadian clock through ubiquitination and stabilization of cryptochromes. Cell. 2013;152:1106-18 pubmed publisher
    ..Previous studies revealed that FBXL3, an F-box-type E3 ligase, ubiquitinates CRYs and mediates their degradation...
  4. Denisenko E, Guler R, Mhlanga M, Suzuki H, Brombacher F, Schmeier S. Transcriptionally induced enhancers in the macrophage immune response to Mycobacterium tuberculosis infection. BMC Genomics. 2019;20:71 pubmed publisher
    ..tb infection, such as Fbxl3, Tapt1, Edn1, and Hivep1...
  5. Wang B, Cheng H, Wang L, Zhou H, Wang J. Expression of ICOSLG on mouse hematologic neoplasm cell lines and their influence on cytotoxicity in allogeneic mixed lymphocyte reactions. Leuk Lymphoma. 2012;53:674-80 pubmed publisher
    ..we examined the expression of ICOSLG in mouse hematologic neoplasm cell lines for the first time and used FBL3/A20 as targets to study...
  6. Correia S, Chan A, Vaughan M, Zolboot N, Perea V, Huber A, et al. The circadian E3 ligase complex SCFFBXL3+CRY targets TLK2. Sci Rep. 2019;9:198 pubmed publisher
    We recently demonstrated that the circadian clock component CRY2 is an essential cofactor in the SCFFBXL3-mediated ubiquitination of c-MYC...
  7. Nangle S, Rosensweig C, Koike N, Tei H, Takahashi J, Green C, et al. Molecular assembly of the period-cryptochrome circadian transcriptional repressor complex. elife. 2014;3:e03674 pubmed publisher
    ..while its C-terminal half flanks the CRY2 C-terminal helix and sterically hinders the recognition of CRY2 by the FBXL3 ubiquitin ligase...
  8. Wang D, Han X, Li C, Bai W. FBXL3 is regulated by miRNA-4735-3p and suppresses cell proliferation and migration in non-small cell lung cancer. Pathol Res Pract. 2019;215:358-365 pubmed publisher
    ..study was to discover the detailed function and molecular mechanism of F-box and leucine rich repeat protein 3 (FBXL3) in NSCLC...
  9. Song N, Gao L, Qiu H, Huang C, Cheng H, Zhou H, et al. Mouse bone marrow-derived mesenchymal stem cells inhibit leukemia/lymphoma cell proliferation in vitro and in a mouse model of allogeneic bone marrow transplant. Int J Mol Med. 2015;36:139-49 pubmed publisher
    ..present study, we co‑cultured C57BL/6 mouse bone marrow (BM)‑derived MSCs with A20 murine B lymphoma, FBL3 murine erythroleukemia and P388 murine acute lymphocytic leukemia cells...

More Information

Publications32

  1. Guo X, Zhu Y, Hong X, Zhang M, Qiu X, Wang Z, et al. miR-181d and c-myc-mediated inhibition of CRY2 and FBXL3 reprograms metabolism in colorectal cancer. Cell Death Dis. 2017;8:e2958 pubmed publisher
    ..Mechanistically, miR-181d stabilized c-myc through directly targeting the 3'-UTRs of CRY2 and FBXL3, which subsequently increased the glucose consumption and the lactate production...
  2. Qiu L, Li J, Yu S, Wang Q, Li Y, Hu Z, et al. A novel cancer immunotherapy based on the combination of a synthetic carbohydrate-pulsed dendritic cell vaccine and glycoengineered cancer cells. Oncotarget. 2015;6:5195-203 pubmed
    ..The results showed that this strategy could significantly inhibit FBL3 tumor growth and prolong the survival of tumor-bearing mice; B16F10 lung metastases could also be reduced...
  3. Papp S, Huber A, Jordan S, Kriebs A, Nguyen M, Moresco J, et al. DNA damage shifts circadian clock time via Hausp-dependent Cry1 stabilization. elife. 2015;4: pubmed publisher
    ..k.a Usp7), stabilizing Cry1 and shifting circadian clock time. DNA damage also increases Cry2 interaction with Fbxl3, destabilizing Cry2...
  4. He S, Liang X, Li L, Sun J, Wen Z, Cheng X, et al. Transcriptome analysis of food habit transition from carnivory to herbivory in a typical vertebrate herbivore, grass carp Ctenopharyngodon idella. BMC Genomics. 2015;16:15 pubmed publisher
    ..Altered expressions of Per, Cry, Clock, Bmal2, Pdp, Dec and Fbxl3 might reset circadian phase of fish after food habit transition...
  5. Wegner S, Belle M, Hughes A, Diekman C, Piggins H. Delayed Cryptochrome Degradation Asymmetrically Alters the Daily Rhythm in Suprachiasmatic Clock Neuron Excitability. J Neurosci. 2017;37:7824-7836 pubmed publisher
    ..Loss-of-function point mutations in a component of this ligase complex, Fbxl3, delay CRY1/2 degradation, reduce circadian rhythm strength, and lengthen the circadian period by ∼2.5 h...
  6. Shi G, Xie P, Qu Z, Zhang Z, Dong Z, An Y, et al. Distinct Roles of HDAC3 in the Core Circadian Negative Feedback Loop Are Critical for Clock Function. Cell Rep. 2016;14:823-834 pubmed publisher
    ..In subjective night, however, HDAC3 blocks FBXL3-mediated CRY1 degradation and strongly promotes BMAL1 and CRY1 association...
  7. Hirano A, Nakagawa T, Yoshitane H, Oyama M, Kozuka Hata H, Lanjakornsiripan D, et al. USP7 and TDP-43: Pleiotropic Regulation of Cryptochrome Protein Stability Paces the Oscillation of the Mammalian Circadian Clock. PLoS ONE. 2016;11:e0154263 pubmed publisher
    ..An F-box protein, FBXL3, promotes ubiquitination and degradation of CRYs, while FBXL21, the closest paralog of FBXL3, ubiquitinates CRYs ..
  8. Hu Y, Shmygelska A, Tran D, Eriksson N, Tung J, Hinds D. GWAS of 89,283 individuals identifies genetic variants associated with self-reporting of being a morning person. Nat Commun. 2016;7:10448 pubmed publisher
    ..4 × 10(-8); rs11121022 near PER3, P=2.0 × 10(-8); rs9565309 near FBXL3, P=3.5 × 10(-8). Circadian and phototransduction pathways are enriched in our results...
  9. Kim E, Kim J, Yang S, Suh S, Kim H, Kim C, et al. Draft Genome Sequence of Tetragenococcus halophilus Strain FBL3, a Probiotic Bacterium Isolated from Galchijeot, a Salted Fermented Food, in the Republic of Korea. Genome Announc. 2017;5: pubmed publisher
    i>Tetragenococcus halophilus strain FBL3 is a lactic acid bacterium isolated from galchijeot, a fermented food made from the salted guts of the hairtail fish, in the Republic of Korea. The draft genome of T...
  10. Patton A, Chesham J, Hastings M. Combined Pharmacological and Genetic Manipulations Unlock Unprecedented Temporal Elasticity and Reveal Phase-Specific Modulation of the Molecular Circadian Clock of the Mouse Suprachiasmatic Nucleus. J Neurosci. 2016;36:9326-41 pubmed publisher
    ..SCN of three genetic backgrounds-wild-type, short-period CK1?(Tau/Tau) mutant, and long-period Fbxl3(Afh/Afh) mutant-all responded reversibly to pharmacological manipulation with period-altering compounds: ..
  11. Tong X, Buelow K, Guha A, Rausch R, Yin L. USP2a protein deubiquitinates and stabilizes the circadian protein CRY1 in response to inflammatory signals. J Biol Chem. 2012;287:25280-91 pubmed publisher
    ..The mammalian clock protein, cryptochrome 1 (CRY1), is degraded via the FBXL3-mediated ubiquitination pathway, suggesting that it is also likely to be targeted by the deubiquitination pathway...
  12. Ilyin G, Rialland M, Pigeon C, Guguen Guillouzo C. cDNA cloning and expression analysis of new members of the mammalian F-box protein family. Genomics. 2000;67:40-7 pubmed
    ..We have isolated cDNAs encoding a further 10 mammalian F-box proteins. Five of them (FBL3 to FBL7) share structural similarities with Skp2 and contain C-terminal leucine-rich repeats...
  13. Sasajima H, Nakagawa K, Kashiwayanagi M, Yokosawa H. Polyubiquitination of the B-cell translocation gene 1 and 2 proteins is promoted by the SCF ubiquitin ligase complex containing ?TrCP. Biol Pharm Bull. 2012;35:1539-45 pubmed
    ..Thus, we propose that BTG1 and BTG2 are subjected to polyubiquitination, more efficiently when it is mediated by SCF?TrCP than by SCFSkp2. ..
  14. Kuchay S, Giorgi C, Simoneschi D, Pagan J, Missiroli S, Saraf A, et al. PTEN counteracts FBXL2 to promote IP3R3- and Ca2+-mediated apoptosis limiting tumour growth. Nature. 2017;546:554-558 pubmed publisher
    ..Notably, we provide proof-of-principle that inhibiting IP3R3 degradation in PTEN-deregulated cancers represents a valid therapeutic strategy. ..
  15. Siddiqui S, Lustig A, Carter A, Sankar M, Daimon C, Premont R, et al. Genomic deletion of GIT2 induces a premature age-related thymic dysfunction and systemic immune system disruption. Aging (Albany NY). 2017;9:706-740 pubmed publisher
    ..spleen, thymus and parathymic lobes revealed a systemic alteration of multiple proteins (Dbp, Tef, Per1, Per2, Fbxl3, Ddit4, Sin3a) involved in the multidimensional control of cell cycle clock regulation, cell senescence, cellular ..
  16. Hirano A, Shi G, Jones C, Lipzen A, Pennacchio L, Xu Y, et al. A Cryptochrome 2 mutation yields advanced sleep phase in humans. elife. 2016;5: pubmed publisher
    ..The mutation alters the conformation of CRY2, increasing its accessibility and affinity for FBXL3 (an E3 ubiquitin ligase), thus promoting its degradation...
  17. Huber A, Papp S, Chan A, Henriksson E, Jordan S, Kriebs A, et al. CRY2 and FBXL3 Cooperatively Degrade c-MYC. Mol Cell. 2016;64:774-789 pubmed publisher
    ..Here we describe an unexpected function for the circadian repressor CRY2 as a component of an FBXL3-containing E3 ligase that recruits T58-phosphorylated c-MYC for ubiquitylation...
  18. Korge S, Grudziecki A, Kramer A. Highly Efficient Genome Editing via CRISPR/Cas9 to Create Clock Gene Knockout Cells. J Biol Rhythms. 2015;30:389-95 pubmed publisher
    ..the application of CRISPR/Cas9 genome editing for the generation of an F-box and leucine-rich repeat protein 3 (Fbxl3) knockout in a human cell line...
  19. Chiaur D, Murthy S, Cenciarelli C, Parks W, Loda M, Inghirami G, et al. Five human genes encoding F-box proteins: chromosome mapping and analysis in human tumors. Cytogenet Cell Genet. 2000;88:255-8 pubmed
    ..fluorescence in situ hybridization (FISH) to 10q24 (BTRC alias beta-TRCP/FBW1a), 9q34 (FBXW2 alias FBW2), 13q22 (FBXL3A alias FBL3a), 5p12 (FBXO4 alias FBX4) and 6q25-->q26 (FBXO5 alias FBX5)...
  20. Pierce N, Lee J, Liu X, Sweredoski M, Graham R, Larimore E, et al. Cand1 promotes assembly of new SCF complexes through dynamic exchange of F box proteins. Cell. 2013;153:206-15 pubmed publisher
    ..We suggest that catalyzed protein exchange may be a general feature of dynamic macromolecular machines and propose a hypothesis for how substrates, Nedd8, and Cand1 collaborate to regulate the cellular repertoire of SCF complexes. ..
  21. Xing W, Busino L, Hinds T, Marionni S, Saifee N, Bush M, et al. SCF(FBXL3) ubiquitin ligase targets cryptochromes at their cofactor pocket. Nature. 2013;496:64-8 pubmed publisher
    ..The SCF(FBXL3) ubiquitin ligase complex controls this negative feedback loop by promoting CRY ubiquitination and degradation...
  22. Anand S, Maywood E, Chesham J, Joynson G, Banks G, Hastings M, et al. Distinct and separable roles for endogenous CRY1 and CRY2 within the circadian molecular clockwork of the suprachiasmatic nucleus, as revealed by the Fbxl3(Afh) mutation. J Neurosci. 2013;33:7145-53 pubmed publisher
    ..of CRY1 and CRY2 within circadian timing in vivo, we exploited the N-ethyl-N-nitrosourea-induced afterhours mutant Fbxl3(Afh) to stabilize endogenous CRY...
  23. Yumimoto K, Muneoka T, Tsuboi T, Nakayama K. Substrate binding promotes formation of the Skp1-Cul1-Fbxl3 (SCF(Fbxl3)) protein complex. J Biol Chem. 2013;288:32766-76 pubmed publisher
    ..b>Fbxl3 is an F-box protein that is responsible for the ubiquitylation and consequent degradation of cryptochromes (Crys) ..