Affinage

FBXO32

F-box only protein 32 · UniProt Q969P5

Length
355 aa
Mass
41.6 kDa
Annotated
2026-06-09
100 papers in source corpus 32 papers cited in narrative 31 extracted findings
Cross-family judge vs UniProt: Affinage preferred faithfulness: 4/5 claims corpus-supported (80%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

FBXO32 (Atrogin-1/MAFbx) is a muscle-enriched F-box protein that nucleates an SCF (Skp1-Cul1-Roc1) E3 ubiquitin ligase complex through its F-box domain and directs polyubiquitination of diverse substrates for proteasomal degradation, thereby governing skeletal and cardiac muscle protein homeostasis, autophagy, and cell growth (PMID:11717410). In atrophying muscle it degrades myogenic regulators MyoD (via ubiquitination at K133) and myogenin, and the translation initiation factor eIF3-f (at conserved C-terminal lysines), coupling the ubiquitin-proteasome system to suppression of differentiation and growth; ubiquitination-resistant substrate mutants produce hypertrophy and resist atrophy (PMID:15531760, PMID:18354498, PMID:19073596, PMID:19319192, PMID:19631210). Its transcription is the principal control node: FOXO3/FOXO4 factors activate the promoter and are repressed by IGF-1/PI3K/Akt signaling, while p38β MAPK phosphorylates C/EBPβ at Thr-188 to drive promoter binding during inflammatory and cachectic wasting, and Smad3 (downstream of TGF-β/myostatin and Pak1) activates the promoter to inhibit mTOR-dependent protein synthesis (PMID:15109499, PMID:15100091, PMID:21847090, PMID:23046544, PMID:18701653, PMID:24002653, PMID:26483344). In the heart, FBXO32 maintains proteostasis and autophagy by degrading the ESCRT component CHMP2B and restrains calcineurin/NFAT-driven hypertrophy, and loss-of-function mutations that disrupt SCF assembly cause dilated cardiomyopathy through impaired autophagy and CHOP-mediated apoptosis (PMID:24789905, PMID:24650875, PMID:26753747, PMID:34272480). Beyond muscle, FBXO32 ubiquitinates substrates including c-Myc, KLF4, CtBP1, and PHPT1 to control proliferation, epithelial-mesenchymal transition, and tumor growth, and its expression is epigenetically silenced by EZH2-mediated H3K27me3 (PMID:25944903, PMID:29142217, PMID:28068319, PMID:35411430, PMID:24213577).

Mechanistic history

Synthesis pass · year-by-year structured walk · 20 steps
  1. 2001 High

    Established that FBXO32 is not merely a muscle-atrophy marker but a bona fide E3 ligase scaffold, defining the molecular machinery through which it acts.

    Evidence Molecular cloning and co-immunoprecipitation of Skp1, Roc1, and Cul1 with the F-box domain

    PMID:11717410

    Open questions at the time
    • No substrate identified at this stage
    • Role of the NLS and PDZ-binding domain in function not resolved
  2. 2004 High

    Answered how upstream growth signaling controls FBXO32, placing it as the transcriptional output of FOXO downstream of IGF-1/PI3K/Akt during atrophy.

    Evidence Promoter reporter, constitutively active and dominant-negative Foxo3, in vivo RNAi, and PI3K/Akt inhibitor dissection in mouse muscle and myotubes

    PMID:15100091 PMID:15109499

    Open questions at the time
    • Did not address parallel inflammatory inputs to the promoter
    • Direct FOXO binding sites partially defined
  3. 2004 High

    Provided the first reconstituted demonstration that SCF(MAFbx) is a functional ligase against a defined substrate, linking it mechanistically to suppression of myogenic differentiation.

    Evidence In vitro ubiquitination with purified recombinant SCF(MAFbx), MyoD K133 mutagenesis, LXXLL-motif interaction mapping, and myoblast overexpression

    PMID:15531760

    Open questions at the time
    • In vivo relevance of K133 ubiquitination addressed only later
    • Other myogenic substrates not yet defined
  4. 2005 High

    Identified p38 MAPK as a distinct, Akt-independent route to FBXO32 induction, explaining inflammatory cytokine-driven atrophy.

    Evidence Pharmacological inhibitor dissection (p38 vs ERK/JNK) in C2C12 myotubes plus in vivo TNF-α injection

    PMID:15746179

    Open questions at the time
    • Transcription factor linking p38 to the promoter not identified here
  5. 2008 High

    Expanded the substrate repertoire to the translation apparatus, showing FBXO32 controls muscle size by degrading eIF3-f and mapping the specific lysines required.

    Evidence Overexpression/shRNA, Co-IP, proteasome rescue, deletion and lysine mutagenesis (K5-10R), and in vivo hypertrophy assays

    PMID:18354498 PMID:19073596

    Open questions at the time
    • Direct in vitro reconstitution of eIF3-f ubiquitination limited
    • Interplay with MyoD degradation not resolved
  6. 2008 Medium

    Extended FBXO32 function to cardiac stress signaling by identifying MKP-1 as a substrate whose degradation sustains JNK-driven cardiomyocyte apoptosis, and added a Foxo4-dependent transcriptional input.

    Evidence Co-IP, proteasome and JNK inhibitor rescues in cardiomyocytes; siRNA against Foxo4 in C2C12 myotubes

    PMID:18701653 PMID:19117950

    Open questions at the time
    • No in vitro reconstitution of MKP-1 ubiquitination
    • Foxo4 mechanism shown without reciprocal validation
  7. 2009 High

    Consolidated FBXO32 as the degrader of myogenic transcription factors in vivo, demonstrating MyoD and myogenin degradation drive atrophy and that nuclear shuttling targets these substrates.

    Evidence shRNA knockdown, subcellular fractionation, in vivo MyoD K133R rescue, Co-IP and proteasome rescue for myogenin

    PMID:19319192 PMID:19631210

    Open questions at the time
    • Signals controlling MAFbx nuclear-cytoplasmic shuttling unknown
    • Myogenin ubiquitination not reconstituted
  8. 2009 Medium

    Implicated FBXO32 in cardiac sarcomere quality control by showing selective degradation of truncated but not wild-type cMyBP-C.

    Evidence Adenoviral overexpression in cardiac myocytes, Co-IP, proteasome inhibitor rescue

    PMID:19850579

    Open questions at the time
    • Single lab, no in vitro reconstitution
    • Mechanism of selectivity for truncated substrate unresolved
  9. 2011 High

    Linked FBXO32 to drug-induced and cancer-associated wasting, identifying statin sensitivity via geranylgeranylation and pinning C/EBPβ as the p38-driven promoter activator in cachexia.

    Evidence Atrogin-1 null cells, zebrafish knockdown, geranylgeraniol rescue; promoter reporter, ChIP, C/EBPβ KO mice, p38 inhibitor

    PMID:17992259 PMID:19406843 PMID:21847090

    Open questions at the time
    • Statin-relevant FBXO32 substrate not defined
    • How geranylgeranylation feeds into FBXO32 induction unclear
  10. 2013 High

    Resolved the molecular switch coupling p38 to the FBXO32 promoter, showing p38β specifically phosphorylates C/EBPβ at Thr-188 to enable DNA binding.

    Evidence Tryptic phosphopeptide mapping, C/EBPβ T188A mutagenesis, ChIP, p38α/β siRNA, in vivo TA injection

    PMID:23046544

    Open questions at the time
    • Single lab
    • Integration with FOXO inputs at the promoter not mapped
  11. 2013 Medium

    Identified Smad3/TGF-β signaling as an additional atrophic input acting on the FBXO32 promoter and coordinately suppressing Akt/mTOR protein synthesis.

    Evidence In vivo plasmid transfection, promoter reporter, protein synthesis and mTOR pathway analysis

    PMID:24002653

    Open questions at the time
    • miR-29/PTEN link proposed without direct validation
    • Direct Smad3 promoter binding site defined only later
  12. 2014 High

    Defined FBXO32's cardioprotective role through proteostasis, showing CHMP2B degradation maintains autophagy and that suppression of calcineurin restrains hypertrophy during unloading.

    Evidence Atrogin-1 KO mice, pulsed SILAC proteomics, Co-IP, CHMP2B siRNA rescue; heterotopic transplantation, NFAT reporter, calcineurin inhibitor rescue

    PMID:24650875 PMID:24789905

    Open questions at the time
    • Whether CHMP2B and calcineurin are degraded by the same SCF activity not distinguished
    • Direct in vitro ubiquitination not shown
  13. 2015 Medium

    Extended FBXO32 beyond muscle to growth control and cardiac transcriptional regulation, identifying c-Myc as a substrate in a negative-feedback loop and a Pak1/Smad3 promoter circuit.

    Evidence Co-IP, ubiquitination assay, c-Myc K326R mutagenesis, reporter assays; Pak1 KO mice, ChIP of Smad3 at FBXO32 promoter, berberine rescue

    PMID:25944903 PMID:26483344

    Open questions at the time
    • c-Myc work single lab without in vitro reconstitution
    • Tissue contexts of the c-Myc feedback loop not defined
  14. 2016 Medium

    Broadened FBXO32 into oncogenic signaling and established the disease mechanism, showing it stabilizes CtBP1 to drive EMT and that an SCF-disrupting missense mutation causes dilated cardiomyopathy via impaired autophagy.

    Evidence Co-IP, ubiquitination, fractionation, xenograft for CtBP1; whole-exome sequencing and Co-IP from patient heart tissue for the cardiomyopathy mutation

    PMID:26753747 PMID:29142217

    Open questions at the time
    • CtBP1 stabilization via ubiquitination mechanistically unusual and single-lab
    • Cardiomyopathy mutation from a single family
  15. 2016 Medium

    Revealed a membrane-trafficking and autophagy-biogenesis role independent of classic degradation, showing FBXO32 binds endophilin-A, tubulates membranes, and is required for autophagosome formation.

    Evidence Co-IP, live-cell imaging on clathrin structures and autophagosomes, overexpression/rescue, autophagy flux assays in neurons

    PMID:27720640

    Open questions at the time
    • Whether E3 activity is required for membrane tubulation unclear
    • Single lab
  16. 2017 Medium

    Added KLF4 as a tumor-relevant substrate, mapping the interaction domains and linking degradation to p38 signaling and tumor growth.

    Evidence Genome-wide E3 ligase siRNA screen, Co-IP, domain mapping, ubiquitination assay, p38 inhibitor, in vivo tumor assay

    PMID:28068319

    Open questions at the time
    • No in vitro reconstitution
    • Context determining oncogenic vs tumor-suppressive role unresolved
  17. 2021 Medium

    Mechanistically connected FBXO32 mutation to cardiomyocyte death, identifying ATF2 as a heart substrate whose impaired ubiquitination drives CHOP-mediated apoptosis.

    Evidence Co-IP of ATF2 with FBXO32 from human heart, ubiquitination assay, mutant overexpression, transcriptional profiling

    PMID:34272480

    Open questions at the time
    • Single lab with limited replication
    • Non-canonical CHOP induction pathway not fully defined
  18. 2021 Medium

    Suggested a degradation-independent transcriptional regulatory function by showing FBXO32 partners with the chromatin remodeler SMARCA4 at regulated loci.

    Evidence Co-IP, proteomics, ChIP at FBXO32-regulated loci, transcriptomics after knockdown, in vivo tumor model

    PMID:33462405

    Open questions at the time
    • Whether FBXO32 ubiquitinates SMARCA4 or acts as a cofactor unclear
    • Single lab
  19. 2022 Medium

    Identified PHPT1 as a substrate whose stabilization upon FBXO32 loss activates ERK/MAPK to promote lung cancer proliferation.

    Evidence Co-IP, mass spectrometry, siRNA knockdown, in vitro and in vivo tumor growth assays

    PMID:35411430

    Open questions at the time
    • No in vitro reconstitution
    • Single lab
  20. 2011 Medium

    Established that FBXO32 expression is epigenetically gated, with EZH2-mediated H3K27me3 silencing its pro-apoptotic function in rhabdomyosarcoma, and HDAC1 controlling its atrophic induction.

    Evidence EZH2 siRNA and inhibitor, FBXO32 promoter ChIP for H3K27me3/EZH2, FBXO32 overexpression, in vivo tumor growth; HDAC1 inhibitor in hindlimb-unloaded rats

    PMID:24213577 PMID:31311969

    Open questions at the time
    • Direct chromatin targeting of the FBXO32 locus context-specific
    • How epigenetic and transcription-factor inputs are integrated unknown

Open questions

Synthesis pass · forward-looking unresolved questions
  • It remains unresolved how FBXO32 selects among its many reported substrates across muscle, cardiac, neuronal, and cancer contexts, and which degradation-independent activities (membrane tubulation, chromatin association) require its E3 ligase function.
  • No unifying substrate-recognition code defined
  • Tissue-specific substrate prioritization unknown
  • Structural basis of SCF(MAFbx)-substrate engagement not determined

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0140096 catalytic activity, acting on a protein 10 GO:0016874 ligase activity 3 GO:0060090 molecular adaptor activity 1
Localization
GO:0005634 nucleus 3 GO:0005829 cytosol 1 GO:0031410 cytoplasmic vesicle 1
Pathway
R-HSA-162582 Signal Transduction 5 R-HSA-392499 Metabolism of proteins 5 R-HSA-5357801 Programmed Cell Death 3 R-HSA-9612973 Autophagy 3 R-HSA-397014 Muscle contraction 2
Partners
CHMP2BCUL1EIF3FMYOD1RBX1SH3GL2SKP1SMARCA4
Complex memberships
SCF (Skp1-Cul1-Roc1-FBXO32) E3 ubiquitin ligase

Evidence

Reading pass · 31 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2001 Atrogin-1/FBXO32 contains a functional F-box domain that binds Skp1, and thereby associates with Roc1 and Cul1 to form an SCF-type E3 ubiquitin ligase complex; it also contains a nuclear localization sequence and PDZ-binding domain. Molecular cloning, domain identification, co-immunoprecipitation with SCF complex components (Skp1, Roc1, Cul1) Proceedings of the National Academy of Sciences of the United States of America High 11717410
2004 Foxo3 transcription factor acts on the atrogin-1 promoter to drive its transcription; PI3K/AKT pathway activation inhibits Foxo factors and thereby suppresses atrogin-1 expression. Dominant-negative Foxo or RNAi knockdown of Foxo in vivo prevents starvation-induced atrogin-1 induction and muscle atrophy. Promoter reporter assay, constitutively active Foxo3 overexpression, dominant-negative Foxo construct, RNAi in mouse muscles in vivo, IGF-1/AKT overexpression Cell High 15109499
2004 The purified recombinant SCF(MAFbx) complex ubiquitinates MyoD in vitro in a lysine-dependent manner; mutation of lysine 133 in MyoD prevents its ubiquitination by SCF(MAFbx). MAFbx binds MyoD through an LXXLL motif in MyoD and an inverted LXXLL motif in MAFbx. Overexpression of MAFbx suppresses MyoD-induced differentiation and myotube formation. In vitro ubiquitination reconstitution with purified recombinant SCF(MAFbx), site-directed mutagenesis of MyoD K133, co-immunoprecipitation, overexpression in myoblasts The Journal of biological chemistry High 15531760
2004 IGF-1 suppresses atrogin-1 expression by blocking mRNA synthesis (not by affecting mRNA degradation) through the PI3K/Akt pathway. Inhibition of PI3K-Akt (but not calcineurin-NFAT or MEK-ERK) increased atrogin-1 mRNA and proteolysis. mRNA stability assay, PI3K/Akt pathway inhibition, pathway-specific inhibitors, myotube culture American journal of physiology. Endocrinology and metabolism High 15100091
2005 TNF-α induces atrogin-1/MAFbx expression in skeletal muscle via p38 MAPK signaling; p38 inhibitors (SB203580, curcumin) blunt the TNF-α-induced increase in atrogin-1 mRNA and ubiquitin conjugating activity, whereas ERK and JNK inhibitors do not. Pharmacological inhibitors of p38, ERK, JNK in C2C12 myotubes; in vivo TNF-α injection in mice; ubiquitin conjugating activity assay FASEB journal High 15746179
2008 eIF3-f (eukaryotic initiation factor 3 subunit 5) is a direct substrate of MAFbx/Atrogin-1; MAFbx polyubiquitinates eIF3-f targeting it for proteasomal degradation. Blockade of MAFbx by shRNA prevents eIF3-f degradation during atrophy, and genetic activation of eIF3-f is sufficient to cause hypertrophy and block atrophy in myotubes. Ectopic MAFbx overexpression in myotubes, shRNA knockdown, co-immunoprecipitation, proteasome inhibitor rescue, in vivo hypertrophy assay The EMBO journal High 18354498
2008 MAFbx/Atrogin-1 polyubiquitinates eIF3-f at multiple C-terminal lysine residues (six lysines in the conserved C-terminal domain are required for full polyubiquitination and degradation). Mutation of all six lysines (K5-10R mutant) produces a hypertrophic gain-of-function in cells and in vivo and protects against starvation-induced atrophy. Deletion analysis, site-directed mutagenesis of eIF3-f lysines, in vitro ubiquitination, in vivo overexpression The Journal of biological chemistry High 19073596
2008 Atrogin-1/MAFbx interacts with and ubiquitinates MAPK phosphatase-1 (MKP-1), targeting it for proteasomal degradation. Loss of MKP-1 leads to sustained JNK activation and enhanced cardiomyocyte apoptosis following simulated ischemia/reperfusion. Co-immunoprecipitation, proteasome inhibitor rescue of MKP-1 degradation, JNK inhibitor (SP600125) rescue assay, overexpression in cardiomyocytes The Journal of biological chemistry Medium 19117950
2009 MAFbx targets MyoD for degradation in multiple skeletal muscle atrophy models; MAFbx undergoes cytoplasmic-nuclear shuttling during atrophy and selectively suppresses MyoD. shRNA-mediated MAFbx silencing inhibits MyoD proteolysis. Overexpression of a ubiquitination-deficient MyoD mutant (K133R) prevents atrophy of mouse primary myotubes and skeletal muscle fibers in vivo. shRNA knockdown of MAFbx in myotubes, subcellular fractionation/localization, overexpression of MyoDK133R mutant in vivo, protein degradation assays PloS one High 19319192
2009 MAFbx/Atrogin-1 is identified as the F-box protein responsible for polyubiquitination of myogenin in atrophying myotubes; MAFbx overexpression causes MG132-sensitive (proteasome-dependent) reduction of myogenin. Myogenin contains a MAFbx-recognition motif and physically interacts with MAFbx. Co-immunoprecipitation, overexpression with proteasome inhibitor rescue, myogenin ubiquitination assay FEBS letters Medium 19631210
2009 Atrogin-1 co-immunoprecipitates with truncated (M7t) but not wild-type cardiac myosin-binding protein C (cMyBP-C); overexpression of atrogin-1 decreases M7t-cMyBP-C protein level by ~80% in a proteasome-dependent manner, while leaving wild-type cMyBP-C unaffected. Adenoviral overexpression in cardiac myocytes, co-immunoprecipitation, proteasome inhibitor rescue Cardiovascular research Medium 19850579
2007 Atrogin-1/MAFbx mediates statin-induced muscle damage; lovastatin induces atrogin-1 expression in humans, zebrafish, and mouse myotubes. atrogin-1 null cells are largely spared from lovastatin-induced morphological changes; atrogin-1 knockdown in zebrafish prevents lovastatin-induced muscle fiber damage. Statin damage is linked to inhibition of geranylgeranylation, not cholesterol synthesis. Atrogin-1 null cell lines, zebrafish knockdown, lovastatin treatment, geranylgeraniol/farnesol rescue experiments The Journal of clinical investigation High 17992259 19406843
2011 C/EBPβ is activated downstream of p38 MAPK and binds a specific C/EBPβ-responsive cis-element in the atrogin-1/MAFbx gene promoter to drive its transcription during cancer cachexia. p38α/β MAPK inhibitor blocks C/EBPβ binding and atrogin-1 induction; C/EBPβ-knockout mice are resistant to LLC tumor-induced atrogin-1 upregulation and muscle wasting. Promoter reporter assay, chromatin immunoprecipitation, C/EBPβ knockout mice, p38 MAPK inhibitor, siRNA knockdown in C2C12 myotubes The EMBO journal High 21847090
2012 p38β MAPK, but not p38α, specifically phosphorylates C/EBPβ at Thr-188, which is critical for C/EBPβ DNA-binding activity and subsequent binding to the atrogin-1/MAFbx promoter. A C/EBPβ T188A dominant-negative mutant blocks atrogin-1 upregulation; this effect is absent in C/EBPβ-null mice. Tryptic phosphopeptide mapping, chromatin immunoprecipitation, site-directed mutagenesis of C/EBPβ, siRNA knockdown of p38α/β, in vivo tibialis anterior injection Skeletal muscle High 23046544
2014 Atrogin-1 targets CHMP2B (charged multivesicular body protein 2B, a component of the ESCRT autophagy complex) for ubiquitin-mediated degradation. Loss of atrogin-1 in KO mice causes CHMP2B accumulation, impaired autophagy, intracellular protein aggregate accumulation, UPR activation, cardiomyocyte apoptosis, and progressive cardiomyopathy. CHMP2B downregulation in atrogin-1 KO mice restores autophagy. Atrogin-1 KO mice, in vivo pulsed SILAC proteomics, co-immunoprecipitation, biochemical fractionation, CHMP2B siRNA rescue The Journal of clinical investigation High 24789905
2014 MAFbx/Atrogin-1 is required for atrophic remodeling of the unloaded heart; MAFbx/Atrogin-1 KO hearts undergo hypertrophy instead of atrophy following mechanical unloading (heterotopic transplantation). In KO hearts, calcineurin accumulates and NFAT transcriptional activity and protein synthesis rates are increased; calcineurin inhibition normalizes NFAT activity. MAFbx/Atrogin-1 thus suppresses calcineurin-driven hypertrophy during unloading. MAFbx/Atrogin-1 KO mice, heterotopic heart transplantation model, calcineurin protein measurement, NFAT luciferase reporter, protein synthesis measurement, calcineurin inhibitor rescue Journal of molecular and cellular cardiology High 24650875
2015 FBXO32/Atrogin-1 targets c-Myc for ubiquitination and proteasomal degradation; mutation of lysine 326 in c-Myc reduces ubiquitination and prevents FBXO32-induced degradation. Phosphorylation of c-Myc at Thr-58/Ser-62 is dispensable for FBXO32-mediated degradation. FBXO32 is itself a direct transcriptional target of c-Myc, creating a negative feedback loop. Co-immunoprecipitation, ubiquitination assay, site-directed mutagenesis (c-Myc K326R), luciferase reporter assay, siRNA knockdown The Journal of biological chemistry Medium 25944903
2016 FBXO32 directly ubiquitinates CtBP1, which is required for CtBP1 stability and nuclear retention, enabling epigenetic remodeling and transcriptional induction of CtBP1 target genes that promote epithelial-mesenchymal transition (EMT). FBXO32 knockdown inhibits tumor growth and metastasis in a xenograft model. Co-immunoprecipitation, ubiquitination assay, nuclear/cytoplasmic fractionation, NSG mouse xenograft, transcriptomic analysis Nature communications Medium 29142217
2016 A missense mutation in FBXO32 impairs binding to SCF complex proteins (validated by co-immunoprecipitation in cells expressing mutant protein and in patient heart tissue), leading to autophagy impairment and dilated cardiomyopathy. Patient hearts show accumulation of proteins regulating autophagy. Co-immunoprecipitation from patient heart tissue and transfected cells, whole exome sequencing, protein accumulation assay Genome biology Medium 26753747
2016 FBXO32/Atrogin-1 interacts with all three endophilin-A proteins; FBXO32 overexpression triggers apoptosis in neurons, but co-expression of endophilin-A rescues this. FBXO32 tubulates membranes and localizes on clathrin-coated structures and transiently co-localizes with autophagosomes. Both FBXO32 and endophilin-A are required for autophagosome formation. Co-immunoprecipitation, live cell imaging (localization on clathrin-coated structures and autophagosomes), overexpression/rescue experiments, autophagy flux assay Cell reports Medium 27720640
2017 FBXO32 physically interacts with the N-terminus (1–60 aa) of KLF4 via its C-terminus (228–355 aa), and the F-box domain is required for FBXO32-dependent KLF4 ubiquitination and degradation. p38 MAPK pathway activity is implicated in this process, as p38 inhibitor abrogates KLF4 ubiquitination. Genome-wide E3 ligase siRNA screen, co-immunoprecipitation, domain mapping, ubiquitination assay, p38 inhibitor treatment, in vivo tumor growth assay Oncogene Medium 28068319
2008 TNF-α increases nuclear Foxo4 protein and atrogin-1 mRNA independently of AKT and Foxo1/Foxo3; siRNA against Foxo4 reduces the TNF-induced increase in atrogin-1 mRNA. TNF does not affect Foxo1/3 nuclear localization despite increasing atrogin-1 expression. PI3K inhibitor (wortmannin), siRNA against Foxo4, IGF stimulation, subcellular fractionation, qRT-PCR in C2C12 myotubes American journal of physiology. Cell physiology Medium 18701653
2013 Smad3 is sufficient to stimulate atrogin-1 promoter activity, inhibit Akt/mTOR signaling and protein synthesis, and induce muscle fiber atrophy in vivo. Smad3-induced inhibition of mTOR is proposed to occur via reduced miR-29 expression and increased PTEN translation. In vivo plasmid transfection (transient transgenic mouse muscle), promoter reporter assay, protein synthesis measurement, mTOR pathway analysis Molecular endocrinology Medium 24002653
2010 FOXO3a mediates crosstalk between PI3K/Akt and MEK/ERK pathways to coordinate atrogin-1 and ubiquitin expression; knockdown of IRS-1 or constitutively active FOXO3a increases IRS-2 protein, MEK/ERK signaling, and ubiquitin expression, linking the two atrogene transcription programs. siRNA knockdown of IRS-1, adenovirus-mediated constitutively active FOXO3a expression, Western blotting, streptozotocin diabetes rat model FASEB journal Medium 20371624
2015 Pak1 activation under pressure overload upregulates Fbxo32 expression through Smad3 binding to an AGAC(-286) site on the FBXO32 promoter. Pharmacological upregulation of Fbxo32 by Berberine ameliorated hypertrophic remodeling in cardiac-specific Pak1 KO mice. Cardiac-specific Pak1 KO mice, constitutively active Pak1 overexpression, chromatin immunoprecipitation (Smad3 binding to FBXO32 promoter), promoter mutagenesis, berberine treatment Hypertension Medium 26483344
2021 Mutant FBXO32 impairs ATF2 ubiquitination; ATF2 protein physically interacts with FBXO32 in the human heart, and expression of mutant FBXO32 is sufficient to induce CHOP-associated apoptosis. FBXO32 mutation causes up-regulation of CHOP and its target genes through a non-canonical pathway. Co-immunoprecipitation of ATF2 with FBXO32 from human heart, ubiquitination assay, overexpression of mutant FBXO32 in cells, transcriptional profiling Communications biology Medium 34272480
2020 Atrogin-1-mediated ubiquitination of aquaporin 4 (AQP4) targets it for degradation in atrophying muscle; AQP4 knockdown reduces myotube size. HMGB1 acts upstream of atrogin-1 via NF-κB signaling to increase atrogin-1 expression. Ubiquitination assay after AQP4 immunoprecipitation, AQP4 knockdown in myotubes, recombinant HMGB1 treatment, NF-κB pathway analysis Scientific reports Medium 32843684
2022 FBXO32 acts as an E3 ubiquitin ligase for PHPT1; knockdown of FBXO32 leads to PHPT1 accumulation and activation of the ERK/MAPK pathway, promoting lung cancer cell proliferation. Co-immunoprecipitation, mass spectrometry, western blotting, siRNA knockdown of FBXO32, in vitro and in vivo tumor growth assays Cellular oncology Medium 35411430
2021 FBXO32 and SMARCA4 (a component of the BAF/PBAF chromatin remodeling complex) physically interact; FBXO32 and SMARCA4 co-localize at loci regulated by FBXO32 (e.g., CDK6), suggesting FBXO32 controls transcription through regulation of chromatin remodeling complex activity. FBXO32 is identified as a MITF target gene. Co-immunoprecipitation, proteomic analysis, ChIP at FBXO32-regulated loci, transcriptomic analysis after FBXO32 knockdown, in vivo tumor model Cell death and differentiation Medium 33462405
2011 EZH2 represses FBXO32 transcription via H3K27 trimethylation at the FBXO32 promoter in PAX3-FOXO1 alveolar rhabdomyosarcoma; EZH2 depletion causes transcriptional derepression of FBXO32 and FBXO32-dependent apoptosis. Simultaneous knockdown of FBXO32 and EZH2 impairs the pro-apoptotic response. EZH2 siRNA knockdown, FBXO32 promoter ChIP for H3K27me3 and EZH2 occupancy, overexpression of FBXO32, pharmacological EZH2 inhibition, in vivo tumor growth Oncogene Medium 24213577
2019 Atrogin-1/MAFbx mRNA expression in rat soleus muscle under hindlimb unloading is regulated by HDAC1; pharmacological inhibition of HDAC1 (CI-994) prevents the unloading-induced increase in MAFbx and ubiquitin expression, without affecting MuRF-1 expression. HDAC1 inhibitor CI-994 treatment in hindlimb-suspended rats, nuclear fractionation of HDAC1, RT-PCR, Western blotting Scientific reports Medium 31311969

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 2412 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 1406 11717410
2014 Skeletal muscle atrophy and the E3 ubiquitin ligases MuRF1 and MAFbx/atrogin-1. American journal of physiology. Endocrinology and metabolism 863 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 495 15746179
2004 IGF-I stimulates muscle growth by suppressing protein breakdown and expression of atrophy-related ubiquitin ligases, atrogin-1 and MuRF1. American journal of physiology. Endocrinology and metabolism 468 15100091
2004 Degradation of MyoD mediated by the SCF (MAFbx) ubiquitin ligase. The Journal of biological chemistry 307 15531760
2012 Atrogin-1, MuRF-1, and sarcopenia. Endocrine 301 22815045
2008 The initiation factor eIF3-f is a major target for atrogin1/MAFbx function in skeletal muscle atrophy. The EMBO journal 257 18354498
2007 The muscle-specific ubiquitin ligase atrogin-1/MAFbx mediates statin-induced muscle toxicity. The Journal of clinical investigation 241 17992259
2015 The role of E3 ubiquitin-ligases MuRF-1 and MAFbx in loss of skeletal muscle mass. Free radical biology & medicine 207 26738803
2009 Inhibition of atrogin-1/MAFbx mediated MyoD proteolysis prevents skeletal muscle atrophy in vivo. PloS one 164 19319192
2016 Indoxyl sulfate potentiates skeletal muscle atrophy by inducing the oxidative stress-mediated expression of myostatin and atrogin-1. Scientific reports 153 27549031
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
2007 Smoking impairs muscle protein synthesis and increases the expression of myostatin and MAFbx in muscle. American journal of physiology. Endocrinology and metabolism 141 17609255
2011 C/EBPβ mediates tumour-induced ubiquitin ligase atrogin1/MAFbx upregulation and muscle wasting. The EMBO journal 124 21847090
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 120 17971512
2014 Atrogin-1 deficiency promotes cardiomyopathy and premature death via impaired autophagy. The Journal of clinical investigation 119 24789905
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 118 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.) 116 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
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 111 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
2016 Endophilin-A Deficiency Induces the Foxo3a-Fbxo32 Network in the Brain and Causes Dysregulation of Autophagy and the Ubiquitin-Proteasome System. Cell reports 97 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 93 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
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
2009 Atrogin-1 and MuRF1 regulate cardiac MyBP-C levels via different mechanisms. Cardiovascular research 77 19850579
2008 MAFbx/Atrogin-1 controls the activity of the initiation factor eIF3-f in skeletal muscle atrophy by targeting multiple C-terminal lysines. The Journal of biological chemistry 76 19073596
2011 Intake of branched-chain amino acids influences the levels of MAFbx mRNA and MuRF-1 total protein in resting and exercising human muscle. American journal of physiology. Endocrinology and metabolism 74 22127230
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
2013 Suppression of atrogin-1 and MuRF1 prevents dexamethasone-induced atrophy of cultured myotubes. Metabolism: clinical and experimental 71 23866982
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
2008 Testosterone protects against dexamethasone-induced muscle atrophy, protein degradation and MAFbx upregulation. The Journal of steroid biochemistry and molecular biology 66 18436443
2015 FBXO32 Targets c-Myc for Proteasomal Degradation and Inhibits c-Myc Activity. The Journal of biological chemistry 64 25944903
2014 The miR-19a/b family positively regulates cardiomyocyte hypertrophy by targeting atrogin-1 and MuRF-1. The Biochemical journal 64 24117217
2013 The Polycomb group (PcG) protein EZH2 supports the survival of PAX3-FOXO1 alveolar rhabdomyosarcoma by repressing FBXO32 (Atrogin1/MAFbx). Oncogene 59 24213577
2017 FBXO32 promotes microenvironment underlying epithelial-mesenchymal transition via CtBP1 during tumour metastasis and brain development. Nature communications 58 29142217
2004 Myosin isoform expression and MAFbx mRNA levels in hibernating golden-mantled ground squirrels (Spermophilus lateralis). Physiological and biochemical zoology : PBZ 55 15449229
2012 p38β MAPK upregulates atrogin1/MAFbx by specific phosphorylation of C/EBPβ. Skeletal muscle 53 23046544
2011 Resveratrol reverses monocrotaline-induced pulmonary vascular and cardiac dysfunction: a potential role for atrogin-1 in smooth muscle. Vascular pharmacology 53 22146233
2009 Ghrelin inhibits skeletal muscle protein breakdown in rats with thermal injury through normalizing elevated expression of E3 ubiquitin ligases MuRF1 and MAFbx. American journal of physiology. Regulatory, integrative and comparative physiology 52 19211729
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
2014 Simvastatin induces mitochondrial dysfunction and increased atrogin-1 expression in H9c2 cardiomyocytes and mice in vivo. Archives of toxicology 49 25300705
2011 Inhibition of atrogin-1/MAFbx expression by adenovirus-delivered small hairpin RNAs attenuates muscle atrophy in fasting mice. Human gene therapy 49 21126200
2019 Indoxyl sulfate induces myotube atrophy by ROS-ERK and JNK-MAFbx cascades. Chemico-biological interactions 45 30849338
2011 Ghrelin and its analogues, BIM-28131 and BIM-28125, improve body weight and regulate the expression of MuRF-1 and MAFbx in a rat heart failure model. PloS one 45 22102869
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
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
2007 Insulin and amino acid availability regulate atrogin-1 in avian QT6 cells. Biochemical and biophysical research communications 43 17418104
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 Ubiquitin ligases MuRF1 and MAFbx in human skeletal muscle atrophy. Joint bone spine 41 17977773
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
2011 Skeletal muscle 11beta-HSD1 controls glucocorticoid-induced proteolysis and expression of E3 ubiquitin ligases atrogin-1 and MuRF-1. PloS one 37 21304964
2016 FBXO32, encoding a member of the SCF complex, is mutated in dilated cardiomyopathy. Genome biology 36 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
2010 Atrogin-1 affects muscle protein synthesis and degradation when energy metabolism is impaired by the antidiabetes drug berberine. Diabetes 33 20522589
2006 Effects of fasting and refeeding on expression of atrogin-1 and Akt/FOXO signaling pathway in skeletal muscle of chicks. Bioscience, biotechnology, and biochemistry 33 17090921
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 32 20399749
2015 Flavones Inhibit LPS-Induced Atrogin-1/MAFbx Expression in Mouse C2C12 Skeletal Myotubes. Journal of nutritional science and vitaminology 31 26052151
2011 C/EBPβ regulates dexamethasone-induced muscle cell atrophy and expression of atrogin-1 and MuRF1. Journal of cellular biochemistry 30 21381078
2021 L-carnitine ameliorates the muscle wasting of cancer cachexia through the AKT/FOXO3a/MaFbx axis. Nutrition & metabolism 29 34724970
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
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
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 27 24453411
2021 FBXO32 links ubiquitination to epigenetic reprograming of melanoma cells. Cell death and differentiation 26 33462405
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
2020 A subset of microRNAs in the Dlk1-Dio3 cluster regulates age-associated muscle atrophy by targeting Atrogin-1. Journal of cachexia, sarcopenia and muscle 25 32495509
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
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
2015 Smad3 Couples Pak1 With the Antihypertrophic Pathway Through the E3 Ubiquitin Ligase, Fbxo32. Hypertension (Dallas, Tex. : 1979) 21 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 21 24390687
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
2020 Atrogin1-induced loss of aquaporin 4 in myocytes leads to skeletal muscle atrophy. Scientific reports 20 32843684
2019 Atrogin-1/MAFbx mRNA expression is regulated by histone deacetylase 1 in rat soleus muscle under hindlimb unloading. Scientific reports 20 31311969
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
2021 Mutation in FBXO32 causes dilated cardiomyopathy through up-regulation of ER-stress mediated apoptosis. Communications biology 19 34272480
2020 Mountain ginseng inhibits skeletal muscle atrophy by decreasing muscle RING finger protein-1 and atrogin1 through forkhead box O3 in L6 myotubes. Journal of ethnopharmacology 19 33161026
2016 A substitution mutation in cardiac ubiquitin ligase, FBXO32, is associated with an autosomal recessive form of dilated cardiomyopathy. BMC medical genetics 19 26768247
2016 Dysregulation between TRIM63/FBXO32 expression and soleus muscle wasting in diabetic rats: potential role of miR-1-3p, -29a/b-3p, and -133a/b-3p. Molecular and cellular biochemistry 19 28000044
2013 Transcriptional effects of E3 ligase atrogin-1/MAFbx on apoptosis, hypertrophy and inflammation in neonatal rat cardiomyocytes. PloS one 19 23335977
2018 Conessine Treatment Reduces Dexamethasone-Induced Muscle Atrophy by Regulating MuRF1 and Atrogin-1 Expression. Journal of microbiology and biotechnology 18 29724080

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