Affinage

FBXL5

F-box/LRR-repeat protein 5 · UniProt Q9UKA1

Length
691 aa
Mass
78.6 kDa
Annotated
2026-04-28
49 papers in source corpus 19 papers cited in narrative 19 extracted findings

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

FBXL5 is the substrate-recognition subunit of an SCF-type E3 ubiquitin ligase that functions as a dual iron–oxygen sensor controlling cellular iron homeostasis. Its N-terminal hemerythrin-like domain contains a redox-active diiron center whose occupancy and oxidation state govern FBXL5 protein stability, while its C-terminal domain harbors a [2Fe-2S] cluster that, when oxidized under iron- and oxygen-replete conditions, organizes the binding surface for IRP2 recruitment, polyubiquitination, and proteasomal degradation—thereby coordinating expression of iron uptake and storage genes (PMID:22253436, PMID:32126207, PMID:31229404). Genetic deletion of Fbxl5 in mice causes embryonic lethality from iron overload that is rescued by concomitant IRP2 deletion, and tissue-specific knockouts reveal essential roles in hepatic iron homeostasis, hematopoietic stem cell self-renewal, and neural progenitor proliferation (PMID:21907140, PMID:28714470, PMID:28069738). Beyond the IRPs, FBXL5 targets additional substrates—including Snail1, hSSB1, CITED2, and cortactin—for ubiquitin-dependent degradation, linking iron sensing to epithelial–mesenchymal transition, DNA damage signaling, HIF-1α transactivation, and cell migration (PMID:24157836, PMID:25249620, PMID:25956243, PMID:24867096). FBXL5 itself is subject to constitutive turnover promoted by the HECT-type ligase HERC2 and translational suppression by G3BP1, establishing layered feedback control over the iron-sensing circuit (PMID:24778179, PMID:38118197).

Mechanistic history

Synthesis pass · year-by-year structured walk · 14 steps
  1. 2007 Low

    Identifying a first non-IRP substrate established that FBXL5 could function as an F-box protein with conventional SCF E3 ligase activity toward cytoplasmic targets such as the dynactin subunit p150Glued.

    Evidence Co-IP, in vitro pulldown, and overexpression ubiquitination assay in HeLa cells

    PMID:17532294

    Open questions at the time
    • Single-lab overexpression study with no mutagenesis or endogenous-level validation
    • Physiological consequence of p150Glued degradation by FBXL5 uncharacterized
    • No reciprocal IP or domain-mapping reported
  2. 2011 High

    In vivo genetic deletion demonstrated that FBXL5 is essential for mammalian iron homeostasis—its loss causes lethal iron overload rescued specifically by IRP2 co-deletion, placing FBXL5 upstream of IRP2 as the primary degradation pathway.

    Evidence Constitutive and liver-specific Fbxl5 knockout mice with IRP1/IRP2 epistasis analysis

    PMID:21907140

    Open questions at the time
    • Molecular mechanism by which FBXL5 senses iron/oxygen not yet resolved at this stage
    • Tissue-specific roles beyond liver not yet explored
  3. 2012 High

    Structural and biophysical studies resolved how FBXL5 senses iron and oxygen through its N-terminal hemerythrin-like diiron center, revealing that iron depletion induces large conformational changes exposing a degradation signal, while oxygen depletion operates by a distinct mechanism, and that iron is incorporated at synthesis rather than through dynamic exchange.

    Evidence X-ray crystallography, CD, NMR, and iron-binding assays under varying Fe/O₂ conditions

    PMID:22253436 PMID:22648410

    Open questions at the time
    • C-terminal domain sensing mechanism not yet characterized
    • How the diiron-center conformational change triggers FBXL5 degradation machinery unknown
  4. 2012 High

    Independent in vivo confirmation that FBXL5 loss leads to constitutive IRP2 accumulation, with epistasis showing rescue by IRP2 but not IRP1 deletion, solidified the FBXL5-IRP2 axis as the dominant iron-sensing pathway; heterozygote analysis revealed dose-dependent compensation via duodenal DMT-1.

    Evidence Conditional Fbxl5 KO mice, double-KO epistasis, hematological assays

    PMID:23135277

    Open questions at the time
    • Non-hepatic tissue-specific consequences still largely unexplored at this point
  5. 2013 High

    Discovery that FBXL5 localizes to the nucleus and polyubiquitinates the EMT transcription factor Snail1—impairing its DNA binding—expanded FBXL5 function beyond iron sensing to regulation of epithelial–mesenchymal transition, with FBXL5 downregulation upon iron depletion providing a mechanistic link between iron status and EMT.

    Evidence shRNA screening, nuclear fractionation, Co-IP, in-cell ubiquitination, DNA-binding assay

    PMID:24157836

    Open questions at the time
    • In vivo relevance of FBXL5-Snail1 axis in tumor metastasis not tested
    • Whether Snail1 targeting requires iron/oxygen sensing by FBXL5 not directly addressed
  6. 2014 Medium

    Multiple new FBXL5 substrates were identified—hSSB1, CITED2, and cortactin—each requiring specific phosphorylation for recognition, revealing that FBXL5 integrates kinase signaling (ATM, ERK) with ubiquitin-mediated degradation to regulate DNA damage checkpoints, HIF-1α transactivation, and cell migration.

    Evidence Co-IP, in vitro ubiquitination, phospho-site mutagenesis (hSSB1 T117, cortactin S405/S418), BRET/FRET assays for CITED2-p300 interaction

    PMID:24867096 PMID:25249620 PMID:25956243

    Open questions at the time
    • Each substrate–FBXL5 pair reported by a single laboratory
    • No structural basis for how phosphorylation enables FBXL5 recognition
    • Relative contribution of FBXL5 versus other E3 ligases for each substrate unclear
  7. 2014 High

    Identification of the HECT ligase HERC2 as a constitutive negative regulator of FBXL5 abundance revealed a second layer of control: HERC2 ubiquitinates FBXL5 for degradation, and its depletion stabilizes FBXL5 and lowers intracellular labile iron.

    Evidence Mass-spectrometry interactome of FBXL5, reciprocal Co-IP, RNAi knockdown with ferrous iron measurement

    PMID:24778179

    Open questions at the time
    • Whether HERC2-mediated FBXL5 degradation is itself iron- or oxygen-regulated not determined
    • Structural basis of HERC2-FBXL5 interaction unknown
  8. 2017 High

    Tissue-specific knockouts in hematopoietic stem cells and neural progenitors demonstrated that the FBXL5-IRP2 axis is essential for stem/progenitor cell maintenance across multiple lineages, with FBXL5 loss causing iron overload, ROS, and functional impairment rescued by IRP2 suppression.

    Evidence Conditional Fbxl5 KO in HSCs (transplantation, transcriptomics) and nestin-Cre brain KO (histology, pharmacological mTOR inhibition)

    PMID:28069738 PMID:28714470

    Open questions at the time
    • Downstream effectors linking iron overload to stem cell failure not fully resolved
    • mTOR involvement in brain phenotype based solely on pharmacology
  9. 2017 Medium

    Characterization of a feedback circuit showed that impaired cytosolic iron–sulfur cluster assembly (CIA) enhances FBXL5 expression and FBXL5-mediated IRP1 polyubiquitination, while IRP overexpression reciprocally induces FBXL5, establishing a negative feedback loop; IRP1 phosphorylation at Ser-138 is required for iron rescue under CIA impairment.

    Evidence Knockdown of CIA factors (NUBP2, FAM96A) combined with FBXL5 suppression, ubiquitination assay, phospho-site mutagenesis

    PMID:28768766

    Open questions at the time
    • Feedback inferred partly from correlative protein-level changes
    • Direct kinase for IRP1 Ser-138 not identified
  10. 2017 Medium

    Detailed redox characterization of the FBXL5 diiron center showed that oxidation-state transitions are accompanied by conformational changes and iron release, directly coupling the redox chemistry to the structural switch that controls FBXL5 stability.

    Evidence EPR, direct electrochemistry, synchrotron-radiation CD, fluorescence spectroscopy

    PMID:28131773

    Open questions at the time
    • In-cell redox potentials and kinetics not measured
    • How iron release from diiron center connects to FBXL5 ubiquitination machinery still unresolved
  11. 2019 High

    Discovery that the CIA targeting complex (MMS19–FAM96B–CIAO1) physically interacts with FBXL5 in an oxygen-dependent manner resolved how FBXL5 acquires its functional [2Fe-2S] cluster and why hypoxia impairs IRP2 degradation—cluster insertion is oxygen-dependent and rate-limiting.

    Evidence Co-IP, mass spectrometry, hypoxia experiments (21% vs 1% O₂), IRP degradation assays

    PMID:31229404

    Open questions at the time
    • Whether cluster insertion into FBXL5 is the sole rate-limiting step for oxygen sensing not formally demonstrated
    • Direct reconstitution of cluster transfer from CIA to FBXL5 not performed
  12. 2020 High

    A cryo-EM structure of the IRP2–FBXL5–SKP1 ternary complex revealed that the oxidized [2Fe-2S] cluster in the FBXL5 C-terminal domain organizes a loop essential for IRP2 docking, and showed that FBXL5 can sterically dislodge IRP2 from IRE-containing RNA—unifying iron/oxygen sensing, substrate recognition, and mRNA de-repression in a single structural framework.

    Evidence Cryo-EM at near-atomic resolution, EPR spectroscopy, in vitro ubiquitination, mutagenesis

    PMID:32126207

    Open questions at the time
    • Full SCF complex (with Cul1/Rbx1) structure not resolved
    • Structural basis for recognition of non-IRP substrates unknown
  13. 2023 Medium

    Identification of G3BP1 as a translational repressor of FBXL5 mRNA added a post-transcriptional layer of FBXL5 regulation: under arsenite stress, G3BP1 suppresses FBXL5 translation, stabilizes IRP2, and elevates labile iron to promote ferroptosis, expanding the FBXL5 circuit to stress-induced cell death.

    Evidence RNA binding assay, polysome profiling, Co-IP, ubiquitination assay, KO/KD cells, in vivo mouse ferroptosis model

    PMID:38118197

    Open questions at the time
    • Whether G3BP1-mediated translational repression operates under physiological (non-arsenite) conditions unclear
    • Stress granule involvement not directly tested
  14. 2023 Medium

    FBXL5 was shown to target TFEB for ubiquitin-dependent degradation and to be required for mouse oocyte meiotic maturation via CITED2 degradation, extending FBXL5 substrate repertoire to lysosome/autophagy regulation and reproductive biology.

    Evidence Co-IP and ubiquitination assays for TFEB; siRNA knockdown in mouse oocytes with in vitro ubiquitination for CITED2

    PMID:37462473 PMID:37743009

    Open questions at the time
    • TFEB interaction reported by single lab with limited mechanistic depth
    • Whether FBXL5 oocyte function depends on iron sensing not tested
    • In vivo validation of TFEB as physiological FBXL5 substrate lacking

Open questions

Synthesis pass · forward-looking unresolved questions
  • Key unresolved questions include the structural basis by which FBXL5 recognizes its diverse non-IRP substrates, the in vivo relevance of several newer substrates (TFEB, cortactin, p150Glued), and how the hemerythrin diiron-center and [2Fe-2S]-cluster sensing domains are coordinately regulated within the full-length protein to integrate iron and oxygen signals.
  • No structure of full-length FBXL5 or FBXL5 bound to non-IRP substrates
  • Physiological significance of many substrates not tested in vivo
  • Coordinated signaling between N-terminal diiron and C-terminal [2Fe-2S] domains not mechanistically resolved

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0140096 catalytic activity, acting on a protein 6 GO:0140299 molecular sensor activity 3 GO:0060090 molecular adaptor activity 2
Localization
GO:0005634 nucleus 1 GO:0005829 cytosol 1
Pathway
R-HSA-8953897 Cellular responses to stimuli 5 R-HSA-382551 Transport of small molecules 3
Partners
CIAO1HERC2IRP1IRP2MMS19NABP2SKP1SNAI1
Complex memberships
SCF(FBXL5)

Evidence

Reading pass · 19 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2020 The C-terminal substrate-binding domain of FBXL5 harbors a [2Fe2S] cluster in the oxidized state. A cryo-EM structure of the IRP2-FBXL5-SKP1 complex reveals that the cluster organizes the FBXL5 C-terminal loop responsible for recruiting IRP2. IRP2 binding to FBXL5 requires the oxidized state of the [2Fe2S] cluster maintained by ambient oxygen, explaining hypoxia-induced IRP2 stabilization. FBXL5 can also sterically dislodge IRP2 from iron-responsive element RNA to facilitate its turnover. Cryo-EM structure of IRP2-FBXL5-SKP1 complex, EPR spectroscopy, in vitro ubiquitination assay, mutagenesis Molecular cell High 32126207
2012 The N-terminal domain of FBXL5 adopts a hemerythrin-like α-helical bundle fold containing a diiron center. This domain undergoes iron-dependent conformational changes that govern the accessibility of a degradation sequence, controlling FBXL5's own proteasomal degradation in response to cellular iron availability. X-ray crystallography of FBXL5 N-terminal domain, biochemical iron-binding assays, mutagenesis of diiron center residues The Journal of biological chemistry High 22253436
2012 The hemerythrin-like domain of FBXL5 communicates iron and oxygen availability by distinct mechanisms: iron limitation induces substantive structural changes in the domain, whereas oxygen depletion does not trigger the same conformational changes, indicating two separate sensing modes. The domain does not dynamically sample the cellular environment; rather, it incorporates iron primarily at or near the time of its own synthesis. Biophysical characterization (CD, NMR-based structural probes), iron-binding assays under varying O2/Fe conditions The Journal of biological chemistry High 22648410
2011 FBXL5-deficient mice die in utero with excessive iron accumulation. This embryonic lethality is rescued by additional deletion of IRP2 but not IRP1, establishing that the FBXL5-IRP2 axis is the primary in vivo pathway for iron homeostasis control. Liver-specific Fbxl5 deletion leads to deregulated hepatic and systemic iron homeostasis and steatohepatitis, with death from acute liver failure on a high-iron diet. Constitutive and conditional (liver-specific) Fbxl5 knockout mice, genetic rescue by IRP2 deletion (epistasis) Cell metabolism High 21907140
2012 FBXL5 is required for maintenance of cellular and systemic iron homeostasis in vivo. FBXL5-null mice show constitutive IRP2 accumulation and misexpression of IRP2 target genes. Viability is restored by simultaneous IRP2 deletion but not IRP1 deletion. Fbxl5 heterozygotes maintain normal hematological values on a low-iron diet via enhanced IRP2 responsiveness and increased DMT-1 expression in the duodenum. Fbxl5 conditional KO mice, IRP2/IRP1 double-KO epistasis, gene expression analysis, hematological assays The Journal of biological chemistry High 23135277
2019 FBXL5 interacts with the CIA-targeting complex (composed of MMS19, FAM96B, and CIAO1). This interaction promotes the ability of FBXL5 to degrade IRPs, and the interaction is regulated by oxygen tension — robust at 21% O2 but severely diminished at 1% O2 — linking Fe-S cluster assembly machinery to oxygen-dependent IRP degradation. Co-immunoprecipitation, mass spectrometry interactome, hypoxia experiments, IRP degradation assays Molecular cell High 31229404
2014 HERC2 (a large HECT-type ubiquitin ligase) associates with FBXL5 and promotes its constitutive ubiquitin-dependent degradation. Depletion of HERC2 by RNAi or inhibition of the HERC2-FBXL5 interaction stabilizes FBXL5, leading to increased FBXL5 abundance and a subsequent decrease in intracellular ferrous iron content. Proteomics/MS identification of FBXL5-associated proteins, Co-IP, RNAi knockdown, ferrous iron measurement The Journal of biological chemistry High 24778179
2013 FBXL5 localizes to the nucleus where it interacts with the transcription factor Snail1, promoting its polyubiquitination. This impairs Snail1 DNA binding. Although polyubiquitination by FBXL5 occurs in the nucleus, Snail1 is degraded in the cytosol. FBXL5 is downregulated by iron depletion and γ-irradiation, explaining Snail1 stabilization under these conditions. Lats2 kinase phosphorylates Snail1 to prevent its nuclear export without blocking FBXL5-mediated polyubiquitination. shRNA screening, Co-IP, in-cell ubiquitination assays, nuclear fractionation, site-directed mutagenesis Nucleic acids research High 24157836
2017 Conditional deletion of Fbxl5 in mouse hematopoietic stem cells (HSCs) results in cellular iron overload, reduced HSC number, and inability to reconstitute the hematopoietic system. Suppression of IRP2 accumulation in FBXL5-deficient HSCs restores stem cell function, placing the FBXL5-IRP2 axis as the key pathway controlling HSC self-renewal and iron homeostasis. Conditional Fbxl5 KO in HSCs, bone marrow transplantation, transcriptomic analysis, IRP2 suppression rescue Nature communications High 28714470
2017 Brain-specific deletion of Fbxl5 in nestin-expressing neural stem progenitor cells (NSPCs) leads to IRP2 stabilization, iron accumulation, ROS generation, and aberrant NSPC and astroglia proliferation in the cerebral cortex. Pharmacological inhibition implicates aberrant mTOR signaling as the downstream effector of FBXL5 deficiency in the brain. Conditional brain-specific Fbxl5 KO mice, histological analysis, pharmacological mTOR inhibition Molecular and cellular biology Medium 28069738
2017 FBXL5 mediates iron-dependent polyubiquitination of IRP1 when cytosolic Fe-S cluster assembly (CIA) is impaired. A regulatory circuit exists in which impaired CIA activity enhances FBXL5 expression and reduces IRP1/IRP2 levels, while IRP overexpression in turn induces FBXL5 protein level — a negative feedback loop. Phosphorylation of IRP1 at Ser-138 is required for iron rescue when CIA is inhibited. Knockdown of CIA factors (NUBP2, FAM96A) with FBXL5 suppression, polyubiquitination assay, cell viability assay, IRP1 phosphorylation site mutagenesis The Journal of biological chemistry Medium 28768766
2014 FBXL5 interacts with and targets hSSB1 (single-stranded DNA-binding protein 1) for ubiquitination and proteasomal degradation via an SCF(FBXL5) E3 ligase complex. ATM-mediated phosphorylation of hSSB1 at T117 prevents FBXL5-mediated degradation. Overexpression of FBXL5 abrogates ATM signaling and DNA damage checkpoint activation, increasing radiosensitivity. Co-IP, in vitro ubiquitination assay, phospho-site mutagenesis (T117A), overexpression/knockdown with checkpoint assays Nucleic acids research Medium 25249620
2014 FBXL5 interacts with CITED2 and promotes its proteasome-dependent degradation. Depletion of FBXL5 by RNAi increases CITED2 protein levels; FBXL5 overexpression decreases CITED2 and impairs CITED2 interaction with the CH1 domain of p300, thereby enabling HIF-1α N-terminal transactivation domain activity. Co-IP, RNAi knockdown, overexpression with proteasome inhibitor MG132, BRET/FRET interaction assay in living cells Archives of biochemistry and biophysics Medium 25956243
2014 FBXL5 interacts with cortactin and targets it for ERK-dependent, ubiquitin-mediated proteasomal degradation. Phosphorylation of cortactin at Ser405/Ser418 (by ERK) is required for FBXL5-induced degradation; the cortactinS405A/S418A mutant resists FBXL5-induced degradation and displays enhanced gastric cancer cell migration. Co-IP, ubiquitination assay, phospho-site mutagenesis, cell migration assays (scratch wound, transwell) Tumour biology Medium 24867096
2007 FBXL5 interacts with p150Glued (the dynactin subunit responsible for binding dynein and microtubules) in vitro and in vivo, co-localizes with it in the cytoplasm with peri-nuclear enrichment in HeLa cells, and promotes p150Glued polyubiquitination and protein turnover. Co-IP, in vitro pulldown, immunofluorescence co-localization, ubiquitination assay Biochemical and biophysical research communications Low 17532294
2023 FBXL5 directly interacts with transcription factor EB (TFEB) and promotes its ubiquitination-mediated proteasomal degradation, contributing to lipid accumulation in alcoholic fatty liver disease. Co-IP, ubiquitination assay, FBXL5 knockdown with lipid accumulation rescue Cellular signalling Low 37743009
2023 FBXL5 is required for mouse oocyte meiotic maturation; its silencing leads to meiotic failure (reduced GVBD and polar body extrusion rates), aberrant mitochondrial dynamics, ROS overproduction, and abnormal CITED2 accumulation. In vitro ubiquitination assay confirmed that FBXL5 interacts with CITED2 and mediates its degradation via the ubiquitin-proteasome pathway. siRNA knockdown in mouse oocytes, in vitro ubiquitination assay, ROS measurement, immunofluorescence FASEB journal Medium 37462473
2017 Redox properties of FBXL5 diiron center were characterized: redox reactions of the diiron center are accompanied by conformational changes and iron release, and the conformation and function of FBXL5 are tuned by the redox state of the diiron center, linking oxidation state to FBXL5 stability. EPR spectroscopy, direct electrochemistry, synchrotron radiation CD, fluorescence spectroscopy, redox kinetics Archives of biochemistry and biophysics Medium 28131773
2023 G3BP1 stabilizes IRP2 by binding to FBXL5 mRNA and suppressing its translation, thereby reducing FBXL5 protein levels and preventing FBXL5-mediated IRP2 ubiquitination and degradation. This G3BP1-FBXL5-IRP2 axis is activated by sodium arsenite to elevate labile iron and promote ferroptosis. RNA binding assay, polysome profiling/translation assay, Co-IP, ubiquitination assay, KO/KD cell models, in vivo mouse ferroptosis model Journal of hazardous materials Medium 38118197

Source papers

Stage 0 corpus · 49 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
1997 AP1-mediated multidrug resistance in Saccharomyces cerevisiae requires FLR1 encoding a transporter of the major facilitator superfamily. The Journal of biological chemistry 162 9235926
2021 Iron-sulfur cluster deficiency can be sensed by IRP2 and regulates iron homeostasis and sensitivity to ferroptosis independent of IRP1 and FBXL5. Science advances 153 34039609
2011 The FBXL5-IRP2 axis is integral to control of iron metabolism in vivo. Cell metabolism 142 21907140
2020 FBXL5 Regulates IRP2 Stability in Iron Homeostasis via an Oxygen-Responsive [2Fe2S] Cluster. Molecular cell 138 32126207
2001 Multiple Yap1p-binding sites mediate induction of the yeast major facilitator FLR1 gene in response to drugs, oxidants, and alkylating agents. The Journal of biological chemistry 86 11056165
2013 Nuclear ubiquitination by FBXL5 modulates Snail1 DNA binding and stability. Nucleic acids research 84 24157836
2017 iASPP induces EMT and cisplatin resistance in human cervical cancer through miR-20a-FBXL5/BTG3 signaling. Journal of experimental & clinical cancer research : CR 70 28399926
1999 FLR1 gene (ORF YBR008c) is required for benomyl and methotrexate resistance in Saccharomyces cerevisiae and its benomyl-induced expression is dependent on pdr3 transcriptional regulator. Yeast (Chichester, England) 70 10572257
2017 Essential role of FBXL5-mediated cellular iron homeostasis in maintenance of hematopoietic stem cells. Nature communications 64 28714470
2015 FBXL5 inhibits metastasis of gastric cancer through suppressing Snail1. Cellular physiology and biochemistry : international journal of experimental cellular physiology, biochemistry, and pharmacology 62 25832584
2012 Structural and molecular characterization of iron-sensing hemerythrin-like domain within F-box and leucine-rich repeat protein 5 (FBXL5). The Journal of biological chemistry 57 22253436
2007 Yeast adaptation to mancozeb involves the up-regulation of FLR1 under the coordinate control of Yap1, Rpn4, Pdr3, and Yrr1. Biochemical and biophysical research communications 51 18086556
2014 HERC2 targets the iron regulator FBXL5 for degradation and modulates iron metabolism. The Journal of biological chemistry 48 24778179
2014 F-box and leucine-rich repeat protein 5 (FBXL5): sensing intracellular iron and oxygen. Journal of inorganic biochemistry 38 24508277
2014 FBXL5-mediated degradation of single-stranded DNA-binding protein hSSB1 controls DNA damage response. Nucleic acids research 35 25249620
2017 A synergistic role of IRP1 and FBXL5 proteins in coordinating iron metabolism during cell proliferation. The Journal of biological chemistry 34 28768766
2001 Transcriptional activation of FLR1 gene during Saccharomyces cerevisiae adaptation to growth with benomyl: role of Yap1p and Pdr3p. Biochemical and biophysical research communications 34 11162502
2019 An Oxygen-Dependent Interaction between FBXL5 and the CIA-Targeting Complex Regulates Iron Homeostasis. Molecular cell 33 31229404
2012 Hemerythrin-like domain within F-box and leucine-rich repeat protein 5 (FBXL5) communicates cellular iron and oxygen availability by distinct mechanisms. The Journal of biological chemistry 32 22648410
2018 Regulation of cellular iron metabolism: Iron-dependent degradation of IRP by SCFFBXL5 ubiquitin ligase. Free radical biology & medicine 31 30218771
2012 F-box and leucine-rich repeat protein 5 (FBXL5) is required for maintenance of cellular and systemic iron homeostasis. The Journal of biological chemistry 31 23135277
2015 FBXL5 modulates HIF-1α transcriptional activity by degradation of CITED2. Archives of biochemistry and biophysics 26 25956243
2018 miR-1306-3p targets FBXL5 to promote metastasis of hepatocellular carcinoma through suppressing snail degradation. Biochemical and biophysical research communications 25 30219228
2014 FBXL5 targets cortactin for ubiquitination-mediated destruction to regulate gastric cancer cell migration. Tumour biology : the journal of the International Society for Oncodevelopmental Biology and Medicine 25 24867096
2020 How Oxidation of a Unique Iron-Sulfur Cluster in FBXL5 Regulates IRP2 Levels and Promotes Regulation of Iron Metabolism Proteins. Molecular cell 24 32243827
2016 FBXL5 attenuates RhoGDI2-induced cisplatin resistance in gastric cancer cells. European review for medical and pharmacological sciences 23 27383304
2007 FBXL5 interacts with p150Glued and regulates its ubiquitination. Biochemical and biophysical research communications 20 17532294
2017 FBXL5 Inactivation in Mouse Brain Induces Aberrant Proliferation of Neural Stem Progenitor Cells. Molecular and cellular biology 19 28069738
2023 A regulatory module comprising G3BP1-FBXL5-IRP2 axis determines sodium arsenite-induced ferroptosis. Journal of hazardous materials 17 38118197
2018 Leishmania donovani inhibits ferroportin translation by modulating FBXL5-IRP2 axis for its growth within host macrophages. Cellular microbiology 17 29470856
2010 Refining current knowledge on the yeast FLR1 regulatory network by combined experimental and computational approaches. Molecular bioSystems 17 20938527
2019 Oxidative Stress Regulated Iron Regulatory Protein IRP2 Through FBXL5-Mediated Ubiquitination-Proteasome Way in SH-SY5Y Cells. Frontiers in neuroscience 13 30760976
2022 Circular RNA Fbxl5 Regulates Cardiomyocyte Apoptosis During Ischemia Reperfusion Injury via Sponging microRNA-146a. Journal of inflammation research 9 35479829
2011 Ultradian rhythm in the intestine of Caenorhabditis elegans is controlled by the C-terminal region of the FLR-1 ion channel and the hydrophobic domain of the FLR-4 protein kinase. Genes to cells : devoted to molecular & cellular mechanisms 9 21518154
2005 Expression of FLR1 transporter requires phospholipase C and is repressed by Mediator. The Journal of biological chemistry 7 16352614
2013 The MFS-type efflux pump Flr1 induced by Yap1 promotes canthin-6-one resistance in yeast. FEBS letters 6 23912082
2011 Qualitative modelling and formal verification of the FLR1 gene mancozeb response in Saccharomyces cerevisiae. IET systems biology 5 22010757
2019 Association between Fbxl5 gene polymorphisms and partial economic traits in Jinghai Yellow chickens. Archives animal breeding 3 31807618
2024 The F-box protein FBXL-5 governs vitellogenesis and lipid homeostasis in C. elegans. Frontiers in cell and developmental biology 2 38946799
2023 FBXL5 promotes lipid accumulation in alcoholic fatty liver disease by promoting the ubiquitination and degradation of TFEB. Cellular signalling 2 37743009
2022 Yap1-mediated Flr1 expression reveals crosstalk between oxidative stress signaling and caffeine resistance in Saccharomyces cerevisiae. Frontiers in microbiology 2 36504777
2017 Redox sensing molecular mechanism of an iron metabolism regulatory protein FBXL5. Archives of biochemistry and biophysics 2 28131773
2017 Influence of sodium nitroprusside on expressions of FBXL5 and IRP2 in SH-SY5Y cells. Sheng li xue bao : [Acta physiologica Sinica] 2 28638917
2011 Quantitative modeling of the Saccharomyces cerevisiae FLR1 regulatory network using an S-system formalism. Journal of bioinformatics and computational biology 2 21976379
2024 The F-box protein FBXL-5 governs vitellogenesis and lipid homeostasis in C. elegans. bioRxiv : the preprint server for biology 1 38712300
2023 Role of FBXL5 in redox homeostasis and spindle assembly during oocyte maturation in mice. FASEB journal : official publication of the Federation of American Societies for Experimental Biology 1 37462473
2026 MFS-transporter Flr1 is a major drug-efflux transporter in Saccharomyces cerevisiae ascospores. FEMS yeast research 0 41700724
2025 Identification and validation of TUBB, CLTA, and FBXL5 as potential diagnostic markers of postmenopausal osteoporosis. Biomolecules & biomedicine 0 40791155
2025 Targeting FBXL5 to induce ferroptosis and reverse oxaliplatin resistance in iron-rich colorectal cancer. Scientific reports 0 41136490