Affinage

FBXO32

F-box only protein 32 · UniProt Q969P5

Length
355 aa
Mass
41.6 kDa
Annotated
2026-04-28
100 papers in source corpus 24 papers cited in narrative 25 extracted findings

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

FBXO32 (Atrogin-1/MAFbx) is a muscle-enriched F-box protein that functions as the substrate-recognition subunit of SCF-type E3 ubiquitin ligase complexes to control muscle mass, cardiac remodeling, autophagy, and cell growth. It assembles with Skp1, Cul1, and Roc1 to ubiquitinate a broad substrate repertoire—including MyoD (at K133), myogenin, eIF3-f, calcineurin, MKP-1, CHMP2B, c-Myc, KLF4, CtBP1, and PHPT1—thereby directing their proteasomal degradation and linking FBXO32 to skeletal muscle atrophy, cardiac hypertrophy suppression, apoptosis, and tumor biology (PMID:11717410, PMID:15531760, PMID:18354498, PMID:17965779, PMID:19117950, PMID:24789905, PMID:25944903, PMID:28068319, PMID:29142217, PMID:35411430). Beyond canonical K48-linked proteolysis, FBXO32 deposits K63-linked polyubiquitin chains on Foxo1/Foxo3a to coactivate their transcriptional programs, and its own expression is transcriptionally induced by Foxo1/3/4 downstream of PI3K/AKT suppression, by the p38β MAPK–C/EBPβ axis, and by Smad3, creating multiple feedback circuits that couple catabolic signaling to substrate destruction (PMID:15109499, PMID:17965779, PMID:21847090, PMID:23046544, PMID:24002653). Loss-of-function mutations in FBXO32 that impair SCF complex assembly cause dilated cardiomyopathy with accumulation of autophagy-regulating proteins, consistent with its role in CHMP2B turnover and autophagosome formation (PMID:26753747, PMID:24789905).

Mechanistic history

Synthesis pass · year-by-year structured walk · 13 steps
  1. 2001 High

    Identification of FBXO32 as an F-box protein that assembles into SCF E3 ligase complexes established the molecular framework for understanding its ubiquitin ligase function in muscle.

    Evidence Molecular cloning and co-immunoprecipitation showing Skp1/Cul1/Roc1 binding in vitro

    PMID:11717410

    Open questions at the time
    • No substrate had yet been identified
    • Ubiquitin chain type not determined
    • In vivo requirement for SCF assembly not tested
  2. 2004 High

    Discovery that Foxo3 transcriptionally induces FBXO32 downstream of PI3K/AKT suppression revealed the signaling axis controlling FBXO32 expression during muscle atrophy, while identification of MyoD as a direct ubiquitination substrate (at K133) via reconstituted SCF(MAFbx) provided the first mechanistic link between FBXO32 and muscle differentiation/wasting.

    Evidence Promoter reporters with Foxo3 constructs and RNAi in mouse muscle in vivo; in vitro ubiquitination with purified SCF(MAFbx) and MyoD K133R mutagenesis

    PMID:15109499 PMID:15531760

    Open questions at the time
    • Whether Foxo1 and Foxo4 contribute equally was unresolved
    • Downstream consequence of MyoD degradation on atrophy phenotype not tested in vivo at this stage
  3. 2005 High

    Demonstration that TNF-α induces FBXO32 through p38 MAPK (but not ERK or JNK) expanded the upstream signaling inputs beyond the Foxo/AKT axis, linking inflammatory cytokine signaling to atrogin-1 transcription.

    Evidence Pharmacological inhibition with isoform-selective MAPK inhibitors in C2C12 myotubes and mouse skeletal muscle in vivo

    PMID:15746179

    Open questions at the time
    • The transcription factor downstream of p38 mediating FBXO32 induction was not yet identified
    • Whether p38α vs p38β was the relevant isoform was unresolved
  4. 2007 High

    Two cardiac functions of FBXO32 were established: it inhibits physiologic hypertrophy by depositing K63-linked ubiquitin chains on Foxo1/Foxo3a to coactivate their transcription, and it suppresses pathologic hypertrophy by degrading calcineurin—demonstrating that FBXO32 uses distinct ubiquitin chain types for non-proteolytic and proteolytic functions.

    Evidence Transgenic overexpression and knockout mice with K63-specific ubiquitin chain analysis; calcineurin degradation in cardiac models

    PMID:17965779

    Open questions at the time
    • The calcineurin degradation mechanism lacked independent reconstitution in this report
    • Whether K63 chains on Foxo factors recruit specific effectors was unknown
  5. 2008 High

    Identification of eIF3-f and MKP-1 as FBXO32 substrates extended its functional scope: eIF3-f degradation mediates translational suppression during skeletal muscle atrophy, while MKP-1 degradation sustains JNK signaling and promotes cardiomyocyte apoptosis after ischemia/reperfusion.

    Evidence MAFbx overexpression/knockdown with eIF3-f protein measurement and genetic rescue in mouse muscle; co-IP, proteasome inhibitor rescue, and JNK inhibitor experiments for MKP-1 in cardiomyocytes; Foxo4 siRNA studies for TNF-α-dependent FBXO32 induction

    PMID:18354498 PMID:18701653 PMID:19117950

    Open questions at the time
    • In vitro ubiquitination of MKP-1 with purified components not shown
    • Whether eIF3-f degradation is the principal mediator of atrophy vs MyoD degradation was unresolved
  6. 2009 High

    In vivo validation that MyoD K133R (ubiquitination-resistant) prevents muscle atrophy established MyoD as a functionally critical FBXO32 substrate; myogenin was identified as an additional myogenic factor targeted by FBXO32, and cytoplasmic-nuclear shuttling of FBXO32 during atrophy was demonstrated.

    Evidence Electroporation of MyoD K133R into mouse muscle fibers; co-IP and polyubiquitination assays for myogenin; subcellular fractionation of FBXO32

    PMID:19319192 PMID:19631210

    Open questions at the time
    • Myogenin ubiquitination site not mapped
    • Mechanism governing FBXO32 nuclear-cytoplasmic shuttling not identified
  7. 2011 High

    Resolution of the p38 MAPK isoform question: p38β (not p38α) phosphorylates C/EBPβ at Thr-188, enabling C/EBPβ binding to the FBXO32 promoter, which drives atrogin-1 transcription in cancer cachexia—C/EBPβ-null mice resist tumor-induced muscle wasting.

    Evidence Tryptic phosphopeptide mapping, ChIP, C/EBPβ T188A mutagenesis, C/EBPβ KO mice, p38α/β isoform-specific inhibitors

    PMID:21847090 PMID:23046544

    Open questions at the time
    • Whether C/EBPβ and Foxo factors cooperate on the FBXO32 promoter was not addressed
    • Isoform-selective p38β inhibitor specificity in vivo not fully validated
  8. 2014 High

    FBXO32's role in autophagy was established: it degrades CHMP2B (ESCRT-III component), and FBXO32-KO hearts accumulate CHMP2B, develop impaired autophagy and protein aggregates leading to cardiomyopathy; separately, FBXO32-KO hearts fail to undergo atrophic remodeling during unloading due to calcineurin/NFAT de-repression.

    Evidence Atrogin-1 KO mice with pulsed SILAC proteomics and CHMP2B knockdown rescue; heterotopic heart transplantation in KO mice with calcineurin inhibitor rescue

    PMID:24650875 PMID:24789905

    Open questions at the time
    • Whether CHMP2B is a direct ubiquitination substrate (in vitro reconstitution) was not demonstrated
    • Relative contribution of autophagy vs proteasomal degradation pathways in KO cardiomyopathy unclear
  9. 2015 High

    Discovery that FBXO32 ubiquitinates c-Myc (at K326) independently of T58/S62 phosphorylation, and that c-Myc transcriptionally activates FBXO32, revealed a negative feedback loop connecting FBXO32 to growth control beyond muscle; Smad3 was shown to stimulate FBXO32 promoter activity via an AGAC element to inhibit Akt/mTOR signaling.

    Evidence c-Myc K326R mutagenesis and ubiquitination assays with promoter/reporter studies; Smad3 promoter mutagenesis with Pak1 KO/OE mice and berberine pharmacology

    PMID:24002653 PMID:25944903 PMID:26483344

    Open questions at the time
    • Whether c-Myc degradation by FBXO32 occurs in muscle or only in non-muscle contexts was unclear
    • Structural basis for phosphorylation-independent c-Myc recognition unknown
  10. 2016 Medium

    A human FBXO32 missense mutation that disrupts SCF complex binding was linked to dilated cardiomyopathy, providing genetic evidence that FBXO32 ligase function is essential for cardiac homeostasis; separately, FBXO32 was found to interact with endophilin-A proteins on clathrin-coated structures and to participate in autophagosome formation in neurons.

    Evidence Co-IP from patient heart tissue showing impaired SCF binding; co-IP and live imaging of FBXO32-endophilin-A with rescue in endophilin-A KO neurons

    PMID:26753747 PMID:27720640

    Open questions at the time
    • The DCM-causing mutation has not been validated by rescue experiment
    • Endophilin-A interaction role in muscle or heart autophagy not tested
    • Whether FBXO32 ubiquitinates endophilin-A or acts as scaffold is unknown
  11. 2017 High

    FBXO32's role was extended to epithelial-mesenchymal transition and cancer: it ubiquitinates CtBP1 to promote its nuclear retention and epigenetic remodeling of EMT genes, and separately ubiquitinates KLF4 for degradation via its C-terminal domain, linking FBXO32 to transcriptional reprogramming in tumor contexts.

    Evidence Ubiquitination assays, subcellular fractionation of CtBP1, in vivo NSG xenograft; genome-wide E3 ligase siRNA screen with KLF4 domain mapping and in vivo tumor assays

    PMID:28068319 PMID:29142217

    Open questions at the time
    • Whether CtBP1 ubiquitination is K63- or K48-linked was not specified
    • Whether FBXO32-CtBP1 axis operates in normal muscle or only in cancer not established
  12. 2021 Medium

    FBXO32 was found to interact with SMARCA4 and co-localize at FBXO32-regulated loci, suggesting a chromatin remodeling mechanism for transcriptional control in melanoma beyond its canonical E3 ligase function.

    Evidence Mass spectrometry interactome, co-IP, ChIP co-localization at CDK6 locus, transcriptomics after FBXO32 knockdown

    PMID:33462405

    Open questions at the time
    • Whether FBXO32 ubiquitinates SMARCA4 or acts as a scaffold is unknown
    • Functional consequence of SMARCA4 interaction not tested by mutagenesis
    • Relevance to muscle or cardiac contexts not examined
  13. 2022 Medium

    PHPT1 was identified as an FBXO32 substrate whose accumulation upon FBXO32 loss activates ERK/MAPK signaling and promotes lung cancer proliferation, extending the substrate repertoire to phosphohistidine signaling.

    Evidence Mass spectrometry substrate identification, knockdown with PHPT1 accumulation, in vitro and in vivo tumor growth assays

    PMID:35411430

    Open questions at the time
    • In vitro ubiquitination with purified components not shown
    • Ubiquitination site on PHPT1 not mapped
    • Whether this mechanism operates in muscle tissue is unknown

Open questions

Synthesis pass · forward-looking unresolved questions
  • Key unresolved questions include the structural basis for FBXO32's broad substrate recognition, the rules governing K48- vs K63-linked chain selection on different substrates, the relative contribution of individual substrates to muscle atrophy and cardiac phenotypes, and whether the chromatin-remodeling and EMT functions of FBXO32 are mechanistically linked to its E3 ligase activity or represent a ligase-independent scaffolding role.
  • No crystal or cryo-EM structure of FBXO32 or SCF(FBXO32)-substrate complex
  • Chain-type selectivity determinants unknown
  • Relative substrate contributions to in vivo phenotypes not genetically dissected

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0140096 catalytic activity, acting on a protein 10 GO:0140110 transcription regulator activity 2
Localization
GO:0005634 nucleus 3 GO:0005829 cytosol 1
Pathway
R-HSA-392499 Metabolism of proteins 10 R-HSA-162582 Signal Transduction 8 R-HSA-397014 Muscle contraction 3 R-HSA-9612973 Autophagy 2 R-HSA-1643685 Disease 1 R-HSA-5357801 Programmed Cell Death 1
Partners
CTBP1CUL1FOXO1FOXO3MYOD1ROC1SKP1SMARCA4
Complex memberships
SCF(FBXO32) (Skp1-Cul1-Roc1-FBXO32)

Evidence

Reading pass · 25 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2001 FBXO32/Atrogin-1 contains a functional F-box domain that binds to Skp1 and thereby to Roc1 and Cul1, forming SCF-type E3 ubiquitin ligase complexes; it also contains a nuclear localization sequence and PDZ-binding domain. Molecular cloning, domain analysis, co-immunoprecipitation with Skp1/Roc1/Cul1 Proceedings of the National Academy of Sciences of the United States of America High 11717410
2004 FBXO32/MAFbx directly ubiquitinates MyoD via an LXXLL motif interaction; the purified recombinant SCF(MAFbx) complex mediates MyoD ubiquitination in vitro in a lysine-dependent pathway (K133 on MyoD), and MAFbx overexpression suppresses MyoD-induced differentiation and myotube formation. In vitro ubiquitination assay with purified recombinant SCF(MAFbx), co-immunoprecipitation, site-directed mutagenesis (MyoD K133R), overexpression in myotubes The Journal of biological chemistry High 15531760
2004 Foxo transcription factors (particularly Foxo3) act on the atrogin-1/FBXO32 promoter to induce its transcription; PI3K/AKT pathway activity suppresses Foxo and thereby suppresses atrogin-1 expression during muscle atrophy. Promoter reporter assays, constitutively active Foxo3 overexpression, dominant-negative Foxo construct, RNAi in mouse muscles in vivo Cell High 15109499
2008 FBXO32/MAFbx targets the eukaryotic initiation factor 3 subunit 5 (eIF3-f) for ubiquitination and proteasomal degradation during muscle atrophy; eIF3-f degradation mediates atrophy downstream of MAFbx, and eIF3-f overexpression is sufficient to cause hypertrophy. Ectopic MAFbx expression in myotubes, shRNA-mediated knockdown of MAFbx, measurement of eIF3-f protein levels, genetic rescue experiments in myotubes and mouse skeletal muscle The EMBO journal High 18354498
2007 FBXO32/Atrogin-1 inhibits Akt-dependent physiologic cardiac hypertrophy by acting as a coactivator for Forkhead (Foxo1 and Foxo3a) transcription factors; this coactivator function depends on FBXO32 ubiquitin ligase activity and deposition of K63-linked polyubiquitin chains on Foxo1/Foxo3a. Transgenic mice overexpressing atrogin-1 in heart, atrogin-1 knockout mice, ubiquitin chain-type analysis (K63-specific), FOXO1 ubiquitylation assays The Journal of clinical investigation High 17965779
2007 FBXO32/Atrogin-1 mediates degradation of calcineurin (a promoter of pathological cardiac hypertrophy) through the ubiquitin ligase complex, thereby inhibiting pathologic cardiac hypertrophy. Referenced in the Li et al. 2007 JCI paper; prior work cited as establishing calcineurin as atrogin-1 substrate The Journal of clinical investigation Medium 17965779
2008 FBXO32/Atrogin-1 interacts with and ubiquitinates MAPK phosphatase-1 (MKP-1), targeting it for proteasomal degradation, thereby causing sustained JNK activation and enhanced cardiomyocyte apoptosis following ischemia/reperfusion injury. Co-immunoprecipitation, overexpression studies, proteasome inhibitor rescue, JNK inhibitor experiments in primary cardiomyocytes The Journal of biological chemistry High 19117950
2009 FBXO32/MAFbx targets myogenin for ubiquitin-mediated proteasomal degradation in the SCF complex; myogenin contains a MAFbx-recognition motif and directly interacts with MAFbx, which activates its polyubiquitination. Co-immunoprecipitation, overexpression with proteasome inhibitor (MG132) rescue, polyubiquitination assay FEBS letters Medium 19631210
2009 In vivo inhibition of MAFbx/FBXO32-mediated MyoD proteolysis (using a MAFbx-ubiquitination-resistant mutant MyoD K133R) prevents skeletal muscle atrophy in mouse primary myotubes and muscle fibers in vivo; MAFbx undergoes cytoplasmic-nuclear shuttling during atrophy. shRNA-mediated MAFbx silencing, overexpression of mutant MyoDK133R, in vivo mouse muscle electroporation, subcellular fractionation/localization PloS one High 19319192
2005 TNF-α stimulates FBXO32/Atrogin-1 gene expression through p38 MAPK signaling pathway in skeletal muscle cells; neither ERK nor JNK pathways mediate this induction. Pharmacological inhibition with SB203580 (p38 inhibitor), PD98059 (ERK inhibitor), SP600125 (JNK inhibitor) in C2C12 myotubes and mouse in vivo injection FASEB journal High 15746179
2011 C/EBPβ, activated by p38β MAPK phosphorylation, binds to a specific cis-element in the atrogin-1/FBXO32 promoter to drive its transcription in cancer cachexia; C/EBPβ-null mice are resistant to tumor-induced atrogin-1 upregulation and muscle wasting. Promoter reporter assays, ChIP assay, C/EBPβ knockout mice, p38α/β isoform-specific inhibitor, siRNA knockdown The EMBO journal High 21847090
2012 p38β MAPK specifically phosphorylates C/EBPβ at Thr-188, a site not phosphorylated by p38α, enabling C/EBPβ binding to the atrogin-1/FBXO32 promoter; p38α does not activate this pathway, explaining the isoform-specific role of p38β in muscle catabolism. Tryptic phosphopeptide mapping, ChIP, constitutively active p38α/β overexpression, site-directed mutagenesis (C/EBPβ T188A), C/EBPβ knockout mice, siRNA knockdown Skeletal muscle High 23046544
2014 FBXO32/Atrogin-1 targets CHMP2B (a component of ESCRT complex required for autophagy) for proteasomal degradation in cardiomyocytes; loss of atrogin-1 leads to CHMP2B accumulation, autophagy impairment, protein aggregate accumulation, and cardiomyopathy. Atrogin-1 KO mice, pulsed SILAC proteomics, biochemical and cellular analyses, CHMP2B knockdown rescue experiment The Journal of clinical investigation High 24789905
2015 FBXO32 targets c-Myc for ubiquitination and proteasomal degradation; FBXO32 interacts with c-Myc, mutation of K326 on c-Myc reduces ubiquitination by FBXO32, and phosphorylation of c-Myc at T58/S62 is dispensable for this degradation. FBXO32 overexpression suppresses c-Myc activity and cell growth, while knockdown promotes it. c-Myc is a direct transcriptional activator of FBXO32, forming a negative feedback loop. Co-immunoprecipitation, ubiquitination assays, site-directed mutagenesis (c-Myc K326R), overexpression and knockdown studies, promoter/reporter assays The Journal of biological chemistry High 25944903
2016 FBXO32 mutation (missense affecting a conserved residue) impairs binding to SCF complex proteins, leading to dilated cardiomyopathy; mutant FBXO32 fails to co-immunoprecipitate with SCF proteins compared to wild-type, and patient hearts show accumulation of autophagy-regulating proteins. Co-immunoprecipitation from cells expressing mutant protein and from patient heart tissue, protein accumulation analysis in DCM patient hearts Genome biology Medium 26753747
2016 FBXO32 interacts with all three endophilin-A proteins, tubulates membranes, localizes on clathrin-coated structures, and colocalizes transiently with autophagosomes; both FBXO32 and endophilin-A are required for autophagosome formation. Coexpression of endophilin-A rescues FBXO32 overexpression-induced apoptosis in cultured neurons. Co-immunoprecipitation, live imaging/colocalization, overexpression/rescue experiments in neurons, genetic mouse model (endophilin-A KO) Cell reports Medium 27720640
2017 FBXO32 directly ubiquitinates CtBP1, which is required for CtBP1 stability and nuclear retention; this enables epigenetic remodeling and transcriptional induction of CtBP1 target genes that create a microenvironment for epithelial-mesenchymal transition (EMT). FBXO32 depletion inhibits tumor growth and metastasis in a mouse xenograft model. Co-immunoprecipitation, ubiquitination assays, subcellular fractionation (CtBP1 nuclear retention), transcriptomic analysis, in vivo NSG xenograft Nature communications High 29142217
2017 FBXO32 mediates KLF4 ubiquitination and degradation through the SCF complex; FBXO32 physically interacts with the N-terminus (1-60 aa) of KLF4 via its C-terminus (228-355 aa). The F-box domain of FBXO32 is required for this activity. p38 MAPK pathway is implicated in FBXO32-mediated KLF4 ubiquitination. Genome-wide E3 ligase siRNA screen, co-immunoprecipitation, ubiquitination assays, domain mapping, p38 inhibitor treatment, colony formation and in vivo tumor assays Oncogene High 28068319
2015 Smad3 binding to a singular AGAC(-286) site on the FBXO32 promoter is required for FBXO32 transcriptional regulation downstream of Pak1 activation; Pak1 promotes FBXO32 expression to suppress cardiac hypertrophy, and pharmacological upregulation of Fbxo32 by berberine ameliorates hypertrophic remodeling in Pak1-deficient mice. Promoter reporter with site-directed mutagenesis (AGAC site), Pak1 cardiac-specific KO and overexpression mice, berberine pharmacological intervention Hypertension Medium 26483344
2013 Smad3 expression is sufficient to stimulate atrogin-1/FBXO32 promoter activity, inhibit Akt/mTOR signaling and protein synthesis, and induce muscle fiber atrophy in vivo; Smad3 also inhibits PGC-1α promoter activity and increases FoxO-mediated signaling. In vivo transient transgenic mouse model (plasmid transfection into muscle), atrogin-1 promoter reporter assay, protein synthesis measurement Molecular endocrinology Medium 24002653
2008 TNF-α increases atrogin-1/FBXO32 mRNA through Foxo4 (not Foxo1/3 or AKT); TNF-α increases nuclear Foxo4 protein, and siRNA targeting Foxo4 reduces TNF-induced atrogin-1 upregulation. siRNA knockdown of Foxo4, nuclear fractionation, AKT inhibitor/activator treatment in C2C12 myotubes American journal of physiology. Cell physiology Medium 18701653
2009 FBXO32/Atrogin-1 co-immunoprecipitates with truncated mutant cardiac myosin-binding protein C (M7t-cMyBP-C) but not wild-type; FBXO32 overexpression in cardiac myocytes decreases M7t-cMyBP-C protein level by 80% via proteasomal degradation, without affecting wild-type cMyBP-C. Co-immunoprecipitation after adenoviral overexpression, proteasome inhibitor rescue, Western blotting Cardiovascular research Medium 19850579
2014 MAFbx/Atrogin-1 is required for atrophic remodeling of the mechanically unloaded heart; in atrogin-1 KO mice, cardiac unloading (heterotopic transplantation) leads to hypertrophy instead of atrophy, driven by calcineurin upregulation and NFAT activation; calcineurin inhibition normalizes NFAT activity and protein synthesis in KO cardiomyocytes. Atrogin-1 KO mice with heterotopic heart transplantation, calcineurin inhibitor treatment, NFAT reporter assay, protein synthesis measurement, human LVAD samples Journal of molecular and cellular cardiology High 24650875
2021 FBXO32 interacts with SMARCA4 (a component of BAF/PBAF chromatin remodeling complexes); FBXO32 and SMARCA4 co-localize at FBXO32-regulated loci (e.g., CDK6), and FBXO32 controls transcription through regulation of chromatin remodeling complex activity in melanoma cells. Proteomic analysis (mass spectrometry), co-immunoprecipitation of SMARCA4, ChIP co-localization, transcriptomic analysis after FBXO32 knockdown Cell death and differentiation Medium 33462405
2022 FBXO32 acts as an E3 ubiquitin ligase for PHPT1; FBXO32 knockdown leads to PHPT1 accumulation, activation of the ERK/MAPK pathway, and promotion of lung cancer cell proliferation and growth. Mass spectrometry, western blotting, knockdown studies, in vitro and in vivo tumor growth assays Cellular oncology Medium 35411430

Source papers

Stage 0 corpus · 100 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2004 Foxo transcription factors induce the atrophy-related ubiquitin ligase atrogin-1 and cause skeletal muscle atrophy. Cell 2390 15109499
2001 Atrogin-1, a muscle-specific F-box protein highly expressed during muscle atrophy. Proceedings of the National Academy of Sciences of the United States of America 1401 11717410
2014 Skeletal muscle atrophy and the E3 ubiquitin ligases MuRF1 and MAFbx/atrogin-1. American journal of physiology. Endocrinology and metabolism 842 25096180
2005 TNF-alpha acts via p38 MAPK to stimulate expression of the ubiquitin ligase atrogin1/MAFbx in skeletal muscle. FASEB journal : official publication of the Federation of American Societies for Experimental Biology 489 15746179
2004 Degradation of MyoD mediated by the SCF (MAFbx) ubiquitin ligase. The Journal of biological chemistry 305 15531760
2012 Atrogin-1, MuRF-1, and sarcopenia. Endocrine 297 22815045
2008 The initiation factor eIF3-f is a major target for atrogin1/MAFbx function in skeletal muscle atrophy. The EMBO journal 256 18354498
2007 The muscle-specific ubiquitin ligase atrogin-1/MAFbx mediates statin-induced muscle toxicity. The Journal of clinical investigation 240 17992259
2007 Atrogin-1 inhibits Akt-dependent cardiac hypertrophy in mice via ubiquitin-dependent coactivation of Forkhead proteins. The Journal of clinical investigation 208 17965779
2015 The role of E3 ubiquitin-ligases MuRF-1 and MAFbx in loss of skeletal muscle mass. Free radical biology & medicine 200 26738803
2006 Atrophy-related ubiquitin ligases, atrogin-1 and MuRF1 are up-regulated in aged rat Tibialis Anterior muscle. Mechanisms of ageing and development 169 16949134
2009 Inhibition of atrogin-1/MAFbx mediated MyoD proteolysis prevents skeletal muscle atrophy in vivo. PloS one 164 19319192
2006 Atrogin-1/MAFbx and MuRF1 are downregulated in aging-related loss of skeletal muscle. The journals of gerontology. Series A, Biological sciences and medical sciences 152 16870627
2016 Indoxyl sulfate potentiates skeletal muscle atrophy by inducing the oxidative stress-mediated expression of myostatin and atrogin-1. Scientific reports 148 27549031
2012 Transforming growth factor-beta induces skeletal muscle atrophy and fibrosis through the induction of atrogin-1 and scleraxis. Muscle & nerve 141 22190307
2007 Smoking impairs muscle protein synthesis and increases the expression of myostatin and MAFbx in muscle. American journal of physiology. Endocrinology and metabolism 138 17609255
2011 C/EBPβ mediates tumour-induced ubiquitin ligase atrogin1/MAFbx upregulation and muscle wasting. The EMBO journal 123 21847090
2014 Atrogin-1 deficiency promotes cardiomyopathy and premature death via impaired autophagy. The Journal of clinical investigation 119 24789905
2007 Repeated resistance exercise training induces different changes in mRNA expression of MAFbx and MuRF-1 in human skeletal muscle. American journal of physiology. Endocrinology and metabolism 118 17971512
2006 Human skeletal muscle atrophy in amyotrophic lateral sclerosis reveals a reduction in Akt and an increase in atrogin-1. FASEB journal : official publication of the Federation of American Societies for Experimental Biology 117 16507768
2003 Induction of MafBx and Murf ubiquitin ligase mRNAs in rat skeletal muscle after LPS injection. FEBS letters 117 12782319
2013 Smad3 induces atrogin-1, inhibits mTOR and protein synthesis, and promotes muscle atrophy in vivo. Molecular endocrinology (Baltimore, Md.) 112 24002653
2004 Role of the insulin-like growth factor I decline in the induction of atrogin-1/MAFbx during fasting and diabetes. Endocrinology 112 15284206
2006 Hormone, cytokine, and nutritional regulation of sepsis-induced increases in atrogin-1 and MuRF1 in skeletal muscle. American journal of physiology. Endocrinology and metabolism 110 17003238
2010 FOXO3a mediates signaling crosstalk that coordinates ubiquitin and atrogin-1/MAFbx expression during glucocorticoid-induced skeletal muscle atrophy. FASEB journal : official publication of the Federation of American Societies for Experimental Biology 108 20371624
2007 AMP-activated protein kinase agonists increase mRNA content of the muscle-specific ubiquitin ligases MAFbx and MuRF1 in C2C12 cells. American journal of physiology. Endocrinology and metabolism 108 17264220
2006 Treatment of rats with calpain inhibitors prevents sepsis-induced muscle proteolysis independent of atrogin-1/MAFbx and MuRF1 expression. American journal of physiology. Regulatory, integrative and comparative physiology 107 16455766
2010 IGF-1 prevents ANG II-induced skeletal muscle atrophy via Akt- and Foxo-dependent inhibition of the ubiquitin ligase atrogin-1 expression. American journal of physiology. Heart and circulatory physiology 97 20228261
2016 Endophilin-A Deficiency Induces the Foxo3a-Fbxo32 Network in the Brain and Causes Dysregulation of Autophagy and the Ubiquitin-Proteasome System. Cell reports 96 27720640
2008 TNF induction of atrogin-1/MAFbx mRNA depends on Foxo4 expression but not AKT-Foxo1/3 signaling. American journal of physiology. Cell physiology 94 18701653
2008 Branched-chain amino acids and arginine suppress MaFbx/atrogin-1 mRNA expression via mTOR pathway in C2C12 cell line. Biochimica et biophysica acta 92 18616983
2008 Atrogin-1/MAFbx enhances simulated ischemia/reperfusion-induced apoptosis in cardiomyocytes through degradation of MAPK phosphatase-1 and sustained JNK activation. The Journal of biological chemistry 89 19117950
2008 Atrogin-1 ubiquitin ligase is upregulated by doxorubicin via p38-MAP kinase in cardiac myocytes. Cardiovascular research 88 18346979
2006 Myocardial expression of Murf-1 and MAFbx after induction of chronic heart failure: Effect on myocardial contractility. Cardiovascular research 88 17145048
2009 Statin-induced muscle damage and atrogin-1 induction is the result of a geranylgeranylation defect. FASEB journal : official publication of the Federation of American Societies for Experimental Biology 87 19406843
2017 Forkhead box O3 plays a role in skeletal muscle atrophy through expression of E3 ubiquitin ligases MuRF-1 and atrogin-1 in Cushing's syndrome. American journal of physiology. Endocrinology and metabolism 76 28246104
2009 Atrogin-1, MuRF1, and FoXO, as well as phosphorylated GSK-3beta and 4E-BP1 are reduced in skeletal muscle of chronic spinal cord-injured patients. Muscle & nerve 76 19533653
2009 Atrogin-1 and MuRF1 regulate cardiac MyBP-C levels via different mechanisms. Cardiovascular research 76 19850579
2007 Curcumin prevents lipopolysaccharide-induced atrogin-1/MAFbx upregulation and muscle mass loss. Journal of cellular biochemistry 74 17131360
2009 Identification of MAFbx as a myogenin-engaged F-box protein in SCF ubiquitin ligase. FEBS letters 73 19631210
2014 Muscle hypertrophy is associated with increases in proteasome activity that is independent of MuRF1 and MAFbx expression. Frontiers in physiology 69 24600408
2012 Branched-chain amino acids reduce hindlimb suspension-induced muscle atrophy and protein levels of atrogin-1 and MuRF1 in rats. Nutrition research (New York, N.Y.) 69 23084640
2017 FBXO32 suppresses breast cancer tumorigenesis through targeting KLF4 to proteasomal degradation. Oncogene 68 28068319
2013 Suppression of atrogin-1 and MuRF1 prevents dexamethasone-induced atrophy of cultured myotubes. Metabolism: clinical and experimental 68 23866982
2008 Testosterone protects against dexamethasone-induced muscle atrophy, protein degradation and MAFbx upregulation. The Journal of steroid biochemistry and molecular biology 66 18436443
2006 Burn-induced increase in atrogin-1 and MuRF-1 in skeletal muscle is glucocorticoid independent but downregulated by IGF-I. American journal of physiology. Regulatory, integrative and comparative physiology 66 16946078
2014 The miR-19a/b family positively regulates cardiomyocyte hypertrophy by targeting atrogin-1 and MuRF-1. The Biochemical journal 64 24117217
2015 FBXO32 Targets c-Myc for Proteasomal Degradation and Inhibits c-Myc Activity. The Journal of biological chemistry 63 25944903
2013 The Polycomb group (PcG) protein EZH2 supports the survival of PAX3-FOXO1 alveolar rhabdomyosarcoma by repressing FBXO32 (Atrogin1/MAFbx). Oncogene 58 24213577
2008 Acute alcohol intoxication increases atrogin-1 and MuRF1 mRNA without increasing proteolysis in skeletal muscle. American journal of physiology. Regulatory, integrative and comparative physiology 58 18401005
2017 FBXO32 promotes microenvironment underlying epithelial-mesenchymal transition via CtBP1 during tumour metastasis and brain development. Nature communications 56 29142217
2004 Myosin isoform expression and MAFbx mRNA levels in hibernating golden-mantled ground squirrels (Spermophilus lateralis). Physiological and biochemical zoology : PBZ 54 15449229
2011 Resveratrol reverses monocrotaline-induced pulmonary vascular and cardiac dysfunction: a potential role for atrogin-1 in smooth muscle. Vascular pharmacology 53 22146233
2012 p38β MAPK upregulates atrogin1/MAFbx by specific phosphorylation of C/EBPβ. Skeletal muscle 51 23046544
2008 Dependence of dexamethasone-induced Akt/FOXO1 signaling, upregulation of MAFbx, and protein catabolism upon the glucocorticoid receptor. Biochemical and biophysical research communications 51 19059383
2011 Inhibition of atrogin-1/MAFbx expression by adenovirus-delivered small hairpin RNAs attenuates muscle atrophy in fasting mice. Human gene therapy 49 21126200
2014 Simvastatin induces mitochondrial dysfunction and increased atrogin-1 expression in H9c2 cardiomyocytes and mice in vivo. Archives of toxicology 48 25300705
2009 Testosterone represses ubiquitin ligases atrogin-1 and Murf-1 expression in an androgen-sensitive rat skeletal muscle in vivo. Journal of applied physiology (Bethesda, Md. : 1985) 45 19926828
2019 Indoxyl sulfate induces myotube atrophy by ROS-ERK and JNK-MAFbx cascades. Chemico-biological interactions 44 30849338
2010 Molecular characterization of atrogin-1/F-box protein-32 (FBXO32) and F-box protein-25 (FBXO25) in rainbow trout (Oncorhynchus mykiss): Expression across tissues in response to feed deprivation. Comparative biochemistry and physiology. Part B, Biochemistry & molecular biology 43 20601059
2008 Modulation of Murf-1 and MAFbx expression in the myocardium by physical exercise training. European journal of cardiovascular prevention and rehabilitation : official journal of the European Society of Cardiology, Working Groups on Epidemiology & Prevention and Cardiac Rehabilitation and Exercise Physiology 43 18525383
2010 Stretching and electrical stimulation reduce the accumulation of MyoD, myostatin and atrogin-1 in denervated rat skeletal muscle. Journal of muscle research and cell motility 42 20191313
2007 Oxidant-induced atrogin-1 and transforming growth factor-beta1 precede alcohol-related myopathy in rats. Muscle & nerve 42 17721978
2009 Eicosapentaenoic acid attenuates arthritis-induced muscle wasting acting on atrogin-1 and on myogenic regulatory factors. American journal of physiology. Regulatory, integrative and comparative physiology 41 19741054
2016 Valproic acid attenuates skeletal muscle wasting by inhibiting C/EBPβ-regulated atrogin1 expression in cancer cachexia. American journal of physiology. Cell physiology 40 27122162
2007 Ubiquitin ligases MuRF1 and MAFbx in human skeletal muscle atrophy. Joint bone spine 40 17977773
2006 IGF-I does not prevent myotube atrophy caused by proinflammatory cytokines despite activation of Akt/Foxo and GSK-3beta pathways and inhibition of atrogin-1 mRNA. American journal of physiology. Endocrinology and metabolism 39 16926385
2011 Skeletal muscle 11beta-HSD1 controls glucocorticoid-induced proteolysis and expression of E3 ubiquitin ligases atrogin-1 and MuRF-1. PloS one 36 21304964
2016 FBXO32, encoding a member of the SCF complex, is mutated in dilated cardiomyopathy. Genome biology 35 26753747
2014 Aberrant methylation and decreased expression of the TGF-β/Smad target gene FBXO32 in esophageal squamous cell carcinoma. Cancer 35 24798237
2018 EZH2 contributes to 5-FU resistance in gastric cancer by epigenetically suppressing FBXO32 expression. OncoTargets and therapy 34 30464532
2017 Oligonol, a Low-Molecular Weight Polyphenol Derived from Lychee, Alleviates Muscle Loss in Diabetes by Suppressing Atrogin-1 and MuRF1. Nutrients 33 28930190
2010 Atrogin-1 affects muscle protein synthesis and degradation when energy metabolism is impaired by the antidiabetes drug berberine. Diabetes 33 20522589
2015 Flavones Inhibit LPS-Induced Atrogin-1/MAFbx Expression in Mouse C2C12 Skeletal Myotubes. Journal of nutritional science and vitaminology 31 26052151
2010 Characterisation and differential regulation of MAFbx/Atrogin-1 alpha and beta transcripts in skeletal muscle of Atlantic salmon (Salmo salar). Biochemical and biophysical research communications 31 20399749
2014 Influence of divergent exercise contraction mode and whey protein supplementation on atrogin-1, MuRF1, and FOXO1/3A in human skeletal muscle. Journal of applied physiology (Bethesda, Md. : 1985) 29 24458747
2021 L-carnitine ameliorates the muscle wasting of cancer cachexia through the AKT/FOXO3a/MaFbx axis. Nutrition & metabolism 28 34724970
2014 MAFbx/Atrogin-1 is required for atrophic remodeling of the unloaded heart. Journal of molecular and cellular cardiology 28 24650875
2010 Systemic IGF-I administration attenuates the inhibitory effect of chronic arthritis on gastrocnemius mass and decreases atrogin-1 and IGFBP-3. American journal of physiology. Regulatory, integrative and comparative physiology 28 20519361
2021 FBXO32 links ubiquitination to epigenetic reprograming of melanoma cells. Cell death and differentiation 26 33462405
2013 TNF- α and IFN-s-dependent muscle decay is linked to NF-κB- and STAT-1α-stimulated Atrogin1 and MuRF1 genes in C2C12 myotubes. Mediators of inflammation 26 24453411
2007 Short bouts of stretching increase myo-D, myostatin and atrogin-1 in rat soleus muscle. Muscle & nerve 26 17143883
2006 Atrophy-related ubiquitin ligases atrogin-1 and MuRF-1 are associated with uterine smooth muscle involution in the postpartum period. American journal of physiology. Regulatory, integrative and comparative physiology 26 17008454
2012 Low-amplitude high frequency vibration down-regulates myostatin and atrogin-1 expression, two components of the atrophy pathway in muscle cells. Journal of tissue engineering and regenerative medicine 25 22711460
2010 Ubiquitin E3 ligase atrogin-1 (Fbox-32) in Atlantic salmon (Salmo salar): sequence analysis, genomic structure and modulation of expression. Comparative biochemistry and physiology. Part B, Biochemistry & molecular biology 25 20728561
2009 Depressed expression of MuRF1 and MAFbx in areas remote of recent myocardial infarction: a mechanism contributing to myocardial remodeling? Basic research in cardiology 25 19859778
2016 Atrogin-1 Deficiency Leads to Myopathy and Heart Failure in Zebrafish. International journal of molecular sciences 24 26840306
2016 Acquired platinum resistance involves epithelial to mesenchymal transition through ubiquitin ligase FBXO32 dysregulation. JCI insight 24 27812537
2012 MAFbx, MuRF1, and the stress-activated protein kinases are upregulated in muscle cells during total knee arthroplasty. American journal of physiology. Regulatory, integrative and comparative physiology 24 22761181
2015 FBXO32, a new TGF-β/Smad signaling pathway target gene, is epigenetically inactivated in gastric cardia adenocarcinoma. Neoplasma 22 25997968
2017 Pyropia yezoensis peptide PYP1‑5 protects against dexamethasone‑induced muscle atrophy through the downregulation of atrogin1/MAFbx and MuRF1 in mouse C2C12 myotubes. Molecular medicine reports 21 28393223
2013 Quadriceps muscle atrophy after anterior cruciate ligament transection involves increased mRNA levels of atrogin-1, muscle ring finger 1, and myostatin. American journal of physical medicine & rehabilitation 21 22854904
2012 Chronic Exercise Training Down-Regulates TNF-α and Atrogin-1/MAFbx in Mouse Gastrocnemius Muscle Atrophy Induced by Hindlimb Unloading. Acta histochemica et cytochemica 21 23378678
2011 SerpinB5 interacts with KHDRBS3 and FBXO32 in gastric cancer cells. Oncology reports 21 21725612
2022 FBXO32 targets PHPT1 for ubiquitination to regulate the growth of EGFR mutant lung cancer. Cellular oncology (Dordrecht, Netherlands) 20 35411430
2019 Atrogin-1/MAFbx mRNA expression is regulated by histone deacetylase 1 in rat soleus muscle under hindlimb unloading. Scientific reports 20 31311969
2015 Smad3 Couples Pak1 With the Antihypertrophic Pathway Through the E3 Ubiquitin Ligase, Fbxo32. Hypertension (Dallas, Tex. : 1979) 20 26483344
2014 Androgenic and estrogenic regulation of Atrogin-1, MuRF1 and myostatin expression in different muscle types of male mice. European journal of applied physiology 20 24390687
2009 Ghrelin receptor agonist, GHRP-2, attenuates burn injury-induced MuRF-1 and MAFbx expression and muscle proteolysis in rats. Peptides 20 19577604
2006 Porcine congenital splayleg is characterised by muscle fibre atrophy associated with relative rise in MAFbx and fall in P311 expression. BMC veterinary research 20 16869957