Affinage

BTRC

F-box/WD repeat-containing protein 1A · UniProt Q9Y297

Length
605 aa
Mass
68.9 kDa
Annotated
2026-04-28
100 papers in source corpus 63 papers cited in narrative 62 extracted findings

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

BTRC (β-TrCP1) encodes the substrate-recognition subunit of the SCF(β-TrCP) E3 ubiquitin ligase, serving as a master regulatory node that couples phosphorylation-dependent substrate recognition to proteasomal degradation across NF-κB signaling, Wnt/β-catenin signaling, cell cycle checkpoints, circadian rhythms, apoptosis, and mTOR pathway regulation. The WD40 repeat domain of β-TrCP binds doubly phosphorylated DSGφXS degrons—and variant motifs such as DDGφXD and TSGXXS—on a broad substrate repertoire including IκBα/β/ε, β-catenin, Cdc25A/B, Emi1, PER2, DEPTOR, Nrf2, p53, Snail, Plk4, STIL, cyclin F, and DMRT1, as established by crystal structure, NMR, and extensive mutagenesis studies (PMID:12820959, PMID:10097128, PMID:10228155, PMID:14603323, PMID:30257202). Upstream kinases (GSK-3β, CK1, IKK, Chk1, CDK1, S6K1, Plk1, CKII) phosphorylate substrate degrons to license β-TrCP binding, creating signaling-responsive degradation switches that control processes from the intra-S-phase DNA damage checkpoint and mitotic entry to mTOR auto-activation and epithelial–mesenchymal transition (PMID:14752276, PMID:22017876, PMID:31209060, PMID:30257202). β-TrCP itself is regulated by SAG/RBX2–CUL5-mediated K11-linked ubiquitination, USP24-dependent deubiquitination, PARP11-mediated mono-ADP-ribosylation, and mutual cross-degradation with β-TrCP2, and is targeted for destruction by viral proteins including rotavirus NSP1 and sequestered by poxvirus A49 as immune evasion strategies (PMID:27906872, PMID:30266897, PMID:30988430, PMID:31406304, PMID:19180189, PMID:23468625).

Mechanistic history

Synthesis pass · year-by-year structured walk · 19 steps
  1. 1999 High

    Identification of β-TrCP as the F-box protein that links phosphorylated IκBα and β-catenin to the SCF ubiquitin ligase complex established it as a phosphodegron-dependent substrate adaptor controlling both NF-κB and Wnt signaling.

    Evidence Co-immunoprecipitation, dominant-negative overexpression, in vitro reconstituted ubiquitination, and Xenopus axis duplication assays across multiple independent labs

    PMID:10075690 PMID:10097128 PMID:10228155 PMID:10339577 PMID:10497169

    Open questions at the time
    • Structural basis of degron recognition not yet resolved
    • Relative contributions of β-TrCP1 vs β-TrCP2 uncharacterized
    • Range of substrates beyond IκB and β-catenin unknown
  2. 1999 High

    Systematic mutagenesis of the DSGφXS motif and flanking residues in IκBα defined the minimal structural requirements for β-TrCP recognition, including an essential acidic Asp31 residue and specific phosphoserine positions.

    Evidence Deletion analysis, site-directed mutagenesis, co-immunoprecipitation, and in vitro ubiquitination assay

    PMID:10514433

    Open questions at the time
    • Three-dimensional structure of the β-TrCP–degron interface not yet available
    • Non-canonical degron variants not yet identified
  3. 2003 High

    The crystal structure of β-TrCP1–Skp1–β-catenin at 3.0 Å revealed how the WD40 propeller recognizes the doubly phosphorylated degron and showed that lysine–degron spacing determines ubiquitination efficiency, providing the first atomic-level understanding of SCF substrate selection.

    Evidence X-ray crystallography, in vitro ubiquitination with mutant β-catenin peptides

    PMID:12820959

    Open questions at the time
    • Structural basis for non-canonical degron variants unresolved
    • How E2 enzyme positioning is controlled at the structural level unclear
  4. 2003 High

    β-TrCP1 knockout mice and NMR of the Vpu–β-TrCP interface revealed essential in vivo roles in cell cycle control (Emi1, centrosome duplication) and confirmed the molecular details of HIV Vpu's hijacking of β-TrCP.

    Evidence Gene knockout in mice with cell cycle phenotyping; NMR (TRNOE/STD) of phospho-Vpu peptide bound to WD40 domain

    PMID:12791266 PMID:12791267 PMID:12843402 PMID:14674748

    Open questions at the time
    • β-TrCP2 compensatory role in knockout only partially addressed
    • Full spectrum of mitotic substrates incomplete
  5. 2003 High

    Extension of β-TrCP substrates to Cdc25A, NF-κB1 p105, and Neurospora FRQ established β-TrCP as a broad-spectrum adaptor regulating DNA damage checkpoints, NF-κB processing, and circadian rhythms.

    Evidence siRNA depletion causing radioresistant DNA synthesis; IKK-dependent phosphorylation and RNAi of β-TrCP blocking p105 processing; FWD1 disruption in Neurospora abolishing circadian rhythms

    PMID:12482991 PMID:12941694 PMID:14603323

    Open questions at the time
    • Circadian role demonstrated in ortholog (Neurospora FWD1), not directly in mammalian β-TrCP
    • Hierarchical kinase priming for Cdc25A not yet fully resolved
  6. 2004 High

    A Chk1→Ser76→Ser82 hierarchical phosphorylation cascade was shown to commit Cdc25A to β-TrCP binding, and Smad4 was identified as a β-TrCP substrate linking it to TGF-β signaling.

    Evidence Chk1 in vitro kinase assay with phospho-mutants for Cdc25A; yeast two-hybrid and co-IP with siRNA for Smad4

    PMID:14752276 PMID:14988407

    Open questions at the time
    • In vivo kinase hierarchy for Cdc25A not validated in animal models
    • Smad4 degron phospho-regulation not fully defined
  7. 2005 High

    Discovery of non-canonical degrons (DDGφXD in Cdc25A/B, DSGIDS in FGD1) expanded the β-TrCP recognition repertoire beyond the canonical phospho-DSGφXS motif.

    Evidence Xenopus egg extract ubiquitination assay with mutagenesis; co-IP and stability assay with FGD1 phospho-mutants

    PMID:15743413 PMID:15845771

    Open questions at the time
    • How WD40 domain accommodates structurally diverse degrons not resolved at atomic level
    • Comprehensive catalog of non-canonical motifs lacking
  8. 2006 High

    β-TrCP was linked to translation control (PDCD4 degradation via S6K1), Hedgehog signaling (Gli2 ubiquitination), pro-caspase-3 turnover, and Emi1 stabilization by Pin1, significantly expanding its functional scope.

    Evidence S6K1 kinase assay and translation reporter for PDCD4; mutagenesis and transcriptional reporter for Gli2; in vitro ubiquitination for pro-caspase-3; Pin1 isomerase competition assay for Emi1

    PMID:16651270 PMID:17053147 PMID:17159919 PMID:17217622

    Open questions at the time
    • Pin1-mediated Emi1 protection mechanism at structural level unresolved
    • Whether β-TrCP controls PDCD4 in all tissue contexts unknown
  9. 2007 High

    GSK-3β-dependent Mcl-1 degradation and PER2 degradation by β-TrCP established critical roles in apoptosis regulation and mammalian circadian clock period determination.

    Evidence In vitro kinase and ubiquitination assays with phospho-dead Mcl-1 mutant; siRNA/dominant-negative β-TrCP with circadian luciferase reporter for PER2

    PMID:17387146 PMID:17876059

    Open questions at the time
    • Whether Mcl-1 degradation by β-TrCP is the dominant pathway vs other E3 ligases not resolved
    • Mathematical modeling of PER2 degradation kinetics not experimentally validated in vivo
  10. 2008 High

    Discovery that β-TrCP mediates Bora destruction (phosphorylated by Plk1/CDK1), GHR endocytosis via a novel UDE motif, and ERK-phosphorylated STAT1 degradation extended the substrate repertoire to mitotic kinase regulation, receptor trafficking, and JAK-STAT signaling.

    Evidence Co-IP with Plk1 phosphorylation and siRNA rescue for Bora; WD40 binding and endocytosis assay for GHR; S727A mutagenesis and siRNA for STAT1

    PMID:17500058 PMID:18378670 PMID:18521620

    Open questions at the time
    • GHR UDE motif interaction not structurally resolved
    • STAT1 as β-TrCP substrate from single lab (Medium confidence)
  11. 2009 High

    β-TrCP was shown to be exploited by HIV-1 Vpu (for BST-2/tetherin degradation) and targeted for destruction by rotavirus NSP1, establishing it as a key node in virus–host conflict; additionally, BimEL and p53 were identified as substrates linking β-TrCP to apoptotic regulation.

    Evidence Vpu DSGxxS mutagenesis with virion release assay; NSP1 transfection with NF-κB reporter; Rsk1/2 kinase cascade for BimEL; IKK2 phosphorylation and dominant-negative β-TrCP for p53

    PMID:19150432 PMID:19180189 PMID:19196987 PMID:19478868

    Open questions at the time
    • Whether p53 degradation by β-TrCP is physiologically significant vs Mdm2 pathway unclear
    • USP47 as a non-substrate interactor's functional role not fully defined
  12. 2011 High

    Three concurrent studies demonstrated that SCF(β-TrCP) degrades DEPTOR upon mTOR/CK1α/RSK1/S6K1-mediated phosphorylation, creating a positive feedback loop for mTOR activation—a critical connection between β-TrCP and mTOR/autophagy regulation. Nrf1 was also identified as a nuclear β-TrCP substrate controlling proteasome gene expression.

    Evidence Co-IP, in vitro phosphorylation reconstitution, degron mutagenesis, mass spectrometry across three independent groups for DEPTOR; siRNA and target gene expression for Nrf1

    PMID:21911472 PMID:22017875 PMID:22017876 PMID:22017877

    Open questions at the time
    • Whether DEPTOR degradation is the sole mechanism for mTOR auto-activation not established
    • Tissue-specific regulation of this feedback loop unknown
  13. 2012 High

    β-TrCP was shown to degrade Nrf2 via GSK-3-dependent phosphorylation of the Neh6 domain, providing a Keap1-independent Nrf2 degradation route, and to degrade HuR via an unconventional IKKα-phosphorylated motif, further expanding non-canonical substrate recognition.

    Evidence Phosphopeptide pulldown and ubiquitylation assay in Keap1-null MEFs for Nrf2; GST pulldown and IKKα kinase assay with novel motif mutagenesis for HuR

    PMID:22964642 PMID:23115237

    Open questions at the time
    • Relative physiological contribution of β-TrCP vs Keap1 to Nrf2 turnover context-dependent and unresolved
    • How IKKα-dependent HuR degradation is triggered by specific stimuli not fully explored
  14. 2013 High

    Poxvirus A49 was found to mimic IκBα's degron to sequester β-TrCP, and MTSS1 was identified as a CKIδ-phosphorylated β-TrCP substrate acting as a tumor suppressor, illustrating both viral subversion and cancer-relevant substrate regulation.

    Evidence A49 DSGxxS mutagenesis with NF-κB reporter and virulence model; CKIδ kinase assay with MTSS1 non-degradable mutant in cancer cell proliferation/migration assays

    PMID:23468625 PMID:24318128

    Open questions at the time
    • Whether A49-like molecular mimicry is used by other pathogens unknown
    • MTSS1 turnover regulation in normal tissue contexts unexplored
  15. 2016 High

    Rotavirus NSP1 was shown to destroy β-TrCP via a hijacked CUL3–RBX1 complex, and β-TrCP1 itself was found to be regulated by SAG/RBX2–CUL5 via K11-linked ubiquitin chains, revealing that β-TrCP stability is actively controlled by other CRL complexes.

    Evidence AP-MS interactome with CUL3/RBX1 siRNA for NSP1 mechanism; ubiquitin chain linkage analysis and E2-specific siRNA for SAG-mediated β-TrCP1 degradation

    PMID:27706223 PMID:27910872

    Open questions at the time
    • Whether K11-linked ubiquitination of β-TrCP1 occurs under physiological stimuli besides viral infection not established
    • CUL3-dependent β-TrCP destruction may involve additional adaptors not yet identified
  16. 2017 High

    β-TrCP was shown to control male germ cell meiotic entry by degrading DMRT1, with double knockout of β-TrCP1/2 causing sterility rescued by Dmrt1 heterozygous deletion, establishing a non-redundant developmental role.

    Evidence Conditional knockout in mouse germ cells, genetic rescue by Dmrt1 heterozygosity, co-IP and ubiquitylation assay

    PMID:28982686

    Open questions at the time
    • Whether β-TrCP controls other germ cell-specific substrates not explored
    • Signaling pathway that activates DMRT1 phosphorylation for β-TrCP recognition not identified
  17. 2018 High

    CKII-phosphorylated cyclin F and CDK2-protected STIL were identified as β-TrCP substrates regulating mitotic entry and centriole number, respectively, consolidating β-TrCP's role as a central cell cycle E3 ligase.

    Evidence CKII kinase assay with TSGXXS mutagenesis for cyclin F; proteomics with MLN4924 and DSG mutagenesis causing centrosome amplification for STIL

    PMID:29445034 PMID:30257202

    Open questions at the time
    • How CDK2 mechanistically shields STIL from β-TrCP not resolved at structural level
    • Whether cyclin F degradation timing varies across cell types unknown
  18. 2019 High

    PARP11-mediated mono-ADP-ribosylation of β-TrCP was found to promote IFNAR1 degradation and suppress interferon signaling, while mutual cross-regulation between β-TrCP1 and β-TrCP2 was demonstrated to control mTORC1 and autophagy through selective DEPTOR/REDD1 degradation.

    Evidence ADP-ribosylation assay with IFNAR1 ubiquitination and antiviral readout; degron mutagenesis and AMPK activation/inhibition with mTORC1 and autophagy assays

    PMID:30988430 PMID:31406304

    Open questions at the time
    • ADP-ribosylation sites on β-TrCP not mapped
    • Whether β-TrCP1/2 mutual regulation is tissue-specific not determined
  19. 2021 High

    β-TrCP/CK1δ-mediated LZTS2 degradation was linked to PI3K/AKT-driven hepatocellular carcinoma, and β-TrCP was identified as the E3 ligase for transferrin receptor TFRC, connecting it to ferroptosis resistance via labile iron pool control.

    Evidence CK1δ kinase assay and tumor models for LZTS2; β-TrCP knockout with ferroptosis and labile iron assays for TFRC

    PMID:33420362 PMID:34315867

    Open questions at the time
    • TFRC as β-TrCP substrate identified by single group with Medium confidence
    • Whether β-TrCP-mediated LZTS2 degradation occurs in non-liver cancers untested

Open questions

Synthesis pass · forward-looking unresolved questions
  • Despite extensive substrate cataloging, no systematic structural basis explains how β-TrCP's WD40 domain accommodates the full spectrum of canonical and non-canonical degrons, and the functional non-redundancy between β-TrCP1 and β-TrCP2 in specific tissues remains incompletely resolved.
  • No co-crystal structures with non-canonical degrons (DDGφXD, UDE, TSGXXS)
  • Tissue-specific and stimulus-specific partitioning of β-TrCP1 vs β-TrCP2 substrates not systematically defined
  • Whether β-TrCP undergoes liquid–liquid phase separation or forms higher-order assemblies for substrate processing unknown

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0140096 catalytic activity, acting on a protein 22 GO:0060090 molecular adaptor activity 4
Localization
GO:0005829 cytosol 3 GO:0005634 nucleus 2
Pathway
R-HSA-162582 Signal Transduction 11 R-HSA-392499 Metabolism of proteins 11 R-HSA-1640170 Cell Cycle 10 R-HSA-168256 Immune System 7 R-HSA-1643685 Disease 6 R-HSA-5357801 Programmed Cell Death 3 R-HSA-9612973 Autophagy 2 R-HSA-9909396 Circadian clock 2 R-HSA-1266738 Developmental Biology 1
Partners
CUL1FBXW11PARP11RASSF1CSKP1TSPAN15USP24USP47
Complex memberships
SCF complex (SKP1-CUL1-F-box)SCF(β-TrCP)

Evidence

Reading pass · 62 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2003 Crystal structure of β-TrCP1–Skp1–β-catenin complex at 3.0 Å resolution revealed that the β-TrCP1 WD40 domain recognizes the doubly phosphorylated DpSGφXpS destruction motif in β-catenin, and established that lysine–destruction motif spacing determines ubiquitination efficiency by increasing effective concentration of substrate lysine at the E2 active site. X-ray crystallography at 3.0 Å, in vitro ubiquitination assay with mutant β-catenin peptides, mutagenesis Molecular Cell High 12820959
1999 FWD1 (mouse β-TrCP ortholog) forms a multi-molecular SCF complex with β-catenin, Axin, GSK-3β, and APC; phosphorylation of β-catenin at the N-terminal destruction motif is required for its association with FWD1; FWD1 facilitates ubiquitination and promotes proteasomal degradation of β-catenin. Co-immunoprecipitation, dominant-negative FWD1 overexpression, ubiquitination assay, β-catenin stability assay The EMBO Journal High 10228155
1999 Phosphorylated β-catenin is specifically recognized by β-Trcp through its F-box/WD40 domain; mutations at critical phosphoserine residues prevent β-Trcp binding; dominant-negative β-Trcp stabilizes β-catenin, activates Wnt signaling, and induces axis duplication in Xenopus embryos. Co-immunoprecipitation, dominant-negative expression, Xenopus embryo axis induction assay PNAS High 10339577
1999 FWD1/β-TrCP is essential for IκBα ubiquitination and proteasomal degradation; FWD1 associates specifically with phosphorylated (Ser32/Ser36) IκBα via the DSGXXS motif; dominant-negative FWD1 blocks NF-κB activation; in vitro reconstitution confirmed SCF-FWD1 ubiquitinates IκBα. Co-immunoprecipitation with phospho-IκBα, dominant-negative overexpression, in vitro ubiquitination assay, NF-κB nuclear translocation assay PNAS High 10097128
1999 h-βTrCP (human ortholog) associates with Ser32/Ser36-phosphorylated IκBα but not unphosphorylated or phosphorylation-deficient mutants; F-box-deleted dominant-negative βTrCP blocks IκBα degradation and NF-κB-dependent transcription. Co-immunoprecipitation, dominant-negative overexpression, NF-κB reporter assay Journal of Biological Chemistry High 10075690
1999 FWD1/β-TrCP mediates ubiquitination of IκBα, IκBβ, and IκBε through recognition of their conserved DSGφXS motif in a phosphorylation-dependent manner; alanine substitution of critical serines abolishes FWD1-mediated ubiquitination. Co-immunoprecipitation, in vitro ubiquitination assay, site-directed mutagenesis Journal of Biological Chemistry High 10497169
1999 Structural requirements for FWD1-IκBα interaction include an acidic residue (Asp31) in the DSGXXS motif in addition to phosphorylation of Ser32/Ser36; Skp1 residues 61–143 are required for FWD1 binding; specific conserved residues in the F-box of FWD1 are dispensable for Skp1 binding. Deletion analysis, site-directed mutagenesis (D31A, G33A, D31E), co-immunoprecipitation, in vitro ubiquitination assay Journal of Biological Chemistry High 10514433
2003 β-TrCP is the F-box protein that targets phosphorylated Cdc25A for degradation by SCF during S phase and in response to DNA damage; siRNA depletion of both β-TrCP1 and β-TrCP2 causes Cdc25A accumulation and radioresistant DNA synthesis, indicating a role in the intra-S-phase checkpoint. siRNA knockdown, co-immunoprecipitation, DNA damage checkpoint assay (radioresistant DNA synthesis) Nature High 14603323
2003 β-Trcp1 knockout in mice causes accumulation of metaphase I spermatocytes, lengthened mitosis, centrosome overduplication, multipolar spindles, and stabilization of cyclin A, cyclin B, and Emi1; Emi1 is identified as a bona fide β-Trcp1 substrate; degradation of β-catenin and IκBα requires additional silencing of β-Trcp2. Gene knockout in mice, siRNA, cell cycle analysis, co-immunoprecipitation, stabilization assay Developmental Cell High 12791266
2003 Emi1 is phosphorylated by Cdc2 on a DSGxxS motif and then recognized and destroyed by SCF(βTrCP/Slimb) in prophase; failure of this destruction stabilizes APC substrates and causes mitotic catastrophe including centrosome overduplication. Co-immunoprecipitation, phosphorylation assay, dominant-negative β-TrCP, mitotic catastrophe phenotypic analysis Developmental Cell High 12791267
2001 βTrCP co-localizes with ATF4 in the nucleus and controls ATF4 stability; the interaction requires ATF4 phosphorylation and Ser219 within a DSGXXXS motif; dominant-negative βTrCP inhibits ATF4 ubiquitination and degradation, enhancing its transcriptional activity. Co-immunoprecipitation, co-localization by immunofluorescence, ubiquitination assay, dominant-negative expression Molecular and Cellular Biology High 11238952
2006 In response to mitogens, PDCD4 is phosphorylated on Ser67 by S6K1, which recruits SCF(βTrCP) for ubiquitination and proteasomal degradation; a stable PDCD4 mutant unable to bind βTrCP inhibits translation of structured 5'UTR mRNAs, causes smaller cell size, and slows cell cycle progression. Co-immunoprecipitation, in vitro kinase assay, stable mutant expression, translation reporter assay, cell size measurement Science High 17053147
2007 GSK-3β phosphorylates Mcl-1 at a STDG consensus motif (Ser155/Ser163), which enables Mcl-1 to associate with β-TrCP; β-TrCP then facilitates Mcl-1 ubiquitination and proteasomal degradation; a phosphorylation-deficient Mcl-1-3A mutant is resistant to degradation and blocks GSK-3β-induced apoptosis. Co-immunoprecipitation, in vitro kinase assay, in vivo ubiquitination assay, stable mutant expression, apoptosis assay Molecular and Cellular Biology High 17387146
2009 Vpu uses its DSGxxS motif (β-TrCP binding site) to recruit β-TrCP and thereby remove BST-2/tetherin from the plasma membrane via AP-2-dependent endocytosis and lysosomal degradation; β-TrCP is required for optimal Vpu-mediated BST-2 downregulation and virion release enhancement. Mutagenesis of Vpu DSGxxS motif, co-immunoprecipitation, flow cytometry of surface BST-2, siRNA depletion, bafilomycin A1 inhibition, virion release assay PLoS Pathogens High 19478868
2009 Rotavirus NSP1 induces proteasome-dependent degradation of β-TrCP, preventing phosphorylated IκBα from being ubiquitinated and thereby blocking NF-κB activation; NSP1 expressed alone in transfected cells is sufficient for this effect. Western blot of β-TrCP after rotavirus infection, NF-κB reporter assay, transient transfection of NSP1, proteasome inhibitor rescue PLoS Pathogens High 19180189
2011 DEPTOR is a physiological substrate of SCF(βTrCP); upon growth factor stimulation RSK1 and S6K1 phosphorylate DEPTOR, enabling βTrCP to bind the degron and ubiquitinate DEPTOR for proteasomal degradation; βTrCP knockdown or degron mutation stabilizes DEPTOR, inactivates mTORC1, and activates autophagy. Co-immunoprecipitation, in vitro kinase assay, ubiquitination assay, dominant-negative βTrCP, siRNA, half-life measurement Molecular Cell High 22017875 22017876 22017877
2011 mTOR and CK1α cooperate to phosphorylate a degron in DEPTOR, generating a phosphodegron that binds βTrCP for ubiquitination and degradation, forming a positive feedback loop for mTOR auto-activation. Co-immunoprecipitation, in vitro phosphorylation assay, mutagenesis of DEPTOR degron, mass spectrometry, siRNA Molecular Cell High 22017875 22017876 22017877
2010 Human Plk4 undergoes βTrCP-dependent proteasomal degradation; Plk4 promotes its own degradation through trans-autophosphorylation within homodimers, generating the βTrCP recognition site; kinase-dead Plk4 blocks trans-autophosphorylation and shields endogenous Plk4 from βTrCP, leading to centriole overduplication. Co-immunoprecipitation, kinase-dead mutant overexpression, centriole counting, centrosome number analysis, proteasome inhibitor assay Journal of Cell Science High 20516151
2009 BimEL is phosphorylated by Rsk1/2 (primed by Erk1/2-mediated Ser69 phosphorylation) on three serines in a conserved degron, enabling binding and ubiquitination by βTrCP and proteasomal degradation; a phosphorylation-deficient BimEL mutant is stable and potently induces apoptosis. Co-immunoprecipitation, in vitro kinase assay, ubiquitination assay, stable mutant expression, apoptosis assay Molecular Cell High 19150432
2008 Plk1 triggers hBora destruction by phosphorylating an SCF(β-TrCP) recognition site on hBora following CDK1-dependent recruitment; Plk1 depletion causes hBora accumulation and Aurora A mislocalization, which is partially rescued by hBora co-depletion. Co-immunoprecipitation, phosphorylation assay, siRNA knockdown, spindle/centrosome phenotype analysis Chromosoma High 18521620
2009 IKK2 phosphorylates p53 at Ser362 and Ser366, recruiting p53 to β-TrCP1 for ubiquitination and Mdm2-independent degradation; siRNA depletion of β-TrCP1 or dominant-negative β-TrCP1 enhances p53 stability; alanine substitutions at Ser362/366 abolish β-TrCP1 binding and stabilize p53. Co-immunoprecipitation, in vitro kinase assay, siRNA, dominant-negative expression, cell cycle analysis PNAS High 19196987
2003 β-TrCP-mediated proteolysis of NF-κB1 p105 requires IKK-dependent phosphorylation of both Ser927 and Ser932 to generate a β-TrCP binding site; depletion of β-TrCP by RNAi blocks TNF-α-induced p105 ubiquitination and proteolysis; β-TrCP binds p105 less efficiently than IκBα. In vitro kinase assay with IKK1/IKK2, RNAi knockdown, phosphopeptide competition binding, co-immunoprecipitation Molecular and Cellular Biology High 12482991
2005 β-TrCP binding and SCF-mediated processing/ubiquitination of NF-κB2/p100 requires NIK/IKKα-dependent phosphorylation of Ser866 and Ser870; mutation of either serine abolishes β-TrCP recruitment and p100 ubiquitination. Co-immunoprecipitation, site-directed mutagenesis, siRNA, ubiquitination assay Cellular Signalling High 16303288
2006 β-TrCP2 directly binds Gli2 and promotes its ubiquitination and proteasomal degradation; a single amino acid substitution in the Gli2 β-TrCP binding site abolishes this interaction, stabilizes Gli2, and increases Gli-dependent transcription. Co-immunoprecipitation, ubiquitination assay, site-directed mutagenesis, transcriptional reporter assay Journal of Biological Chemistry High 16651270
2004 SCF(β-TrCP1) E3 ligase interacts with and ubiquitinates Smad4 for proteasomal degradation; β-TrCP1 interacts with Smad4 in both yeast two-hybrid and mammalian co-IP; overexpression of SCF(β-TrCP1) induces Smad4 ubiquitination; siRNA silencing of β-TrCP1 increases Smad4 protein and enhances TGF-β transcriptional activity. Yeast two-hybrid, co-immunoprecipitation, ubiquitination assay, siRNA, TGF-β reporter assay Journal of Biological Chemistry High 14988407
2003 β-TrCP1 knockout in mice causes impaired IκBα and IκBβ degradation, reduced NF-κB nuclear translocation and DNA binding, altered β-catenin localization, reduced proliferation, increased cell size, and polyploidy in embryonic fibroblasts. Gene knockout in mice, NF-κB EMSA, luciferase reporter, immunofluorescence, flow cytometry PNAS High 12843402
2003 FRQ (Neurospora circadian clock protein, ortholog context: FWD1 is the Neurospora β-TrCP ortholog) physically interacts with FWD1 in vivo; FWD1 disruption severely impairs FRQ degradation and abolishes circadian rhythms; FRQ is likely ubiquitylated in an FWD1-dependent manner. Co-immunoprecipitation, gene disruption, Western blot, circadian conidiation rhythm assay The EMBO Journal Medium 12941694
2007 β-TrCP1 mediates degradation of circadian clock protein PER2; β-TrCP1 knockdown or dominant-negative expression lengthens circadian period; a β-TrCP interaction-deficient PER2 mutant is dramatically stabilized and disrupts circadian rhythmicity due to excessive nuclear repression. siRNA knockdown, dominant-negative expression, luciferase circadian reporter assay, PER2 mutant expression, mathematical modeling Journal of Biological Rhythms High 17876059
2003 NMR analysis of the phosphorylated Vpu peptide bound to β-TrCP revealed that the DpS52GNEpS56 motif makes intimate contact with the WD domain of β-TrCP, with pSer52 showing strongest binding; Ile46 and hydrophobic residues form contacts with a hydrophobic pocket of the WD40 domain. NMR (TRNOE, STD-NMR), molecular dynamics simulation Biochemistry High 14674748
2008 β-TrCP (SCFβTrCP) binds the growth hormone receptor (GHR) through its WD40 domain via a novel UDE motif (not DSGφXS), driving GHR endocytosis and degradation in a neddylation-dependent, ligand-independent manner; TrCP2 silencing is more effective than TrCP1 on GHR degradation. Co-immunoprecipitation, siRNA knockdown, endocytosis assay, neddylation inhibition Journal of Biological Chemistry High 17500058
2005 β-TrCP recognizes a non-phosphorylated DDGφXD motif in both Xenopus Cdc25A and human Cdc25A/Cdc25B; this novel motif is required for β-TrCP-dependent ubiquitination and degradation of Cdc25A/B independently of the canonical DSG motif, and is regulated by nearby residues. Xenopus egg extract ubiquitination assay, mutagenesis, co-immunoprecipitation, cell-based degradation assay PNAS High 15845771
2004 Phosphorylation of Cdc25A at Ser82 (within DSG motif) anchors Cdc25A to β-TrCP; Chk1-dependent phosphorylation at Ser76 serves as a priming step required for Ser82 phosphorylation, establishing a hierarchical phosphorylation cascade that commits Cdc25A to β-TrCP-dependent degradation. Co-immunoprecipitation with phospho-mutants, in vitro Chk1 kinase assay, degradation assay Cell Cycle High 14752276
2012 Nrf2 contains two β-TrCP binding motifs in its Neh6 domain (DSGIS338 and DSAPGS378); deletion of either site decreases β-TrCP-mediated Nrf2 ubiquitylation; the DSGIS motif requires GSK-3-mediated phosphorylation for β-TrCP binding, linking GSK-3 activity to Nrf2 degradation and drug resistance. Biotinylated peptide pulldown, ubiquitylation assay, GSK-3 inhibition/activation, siRNA knockdown, Keap1-null MEFs Oncogene High 22964642
2011 β-TrCP promotes degradation of transcription factor Nrf1 in the nucleus via recognition of a DSGLS motif; siRNA silencing of β-TrCP markedly increases Nrf1 target gene expression (e.g., proteasome subunit PSMC4); cytoplasmic Nrf1 is independently degraded by ERAD ligase Hrd1. siRNA knockdown, ubiquitination assay, mutagenesis, nuclear fractionation, target gene expression Molecular and Cellular Biology High 21911472
2013 Poxvirus protein A49 inhibits NF-κB by molecular mimicry of IκBα: A49 contains an IκBα-like DSGxxS motif that is phosphorylated by IKKβ, binds β-TrCP, and thereby sequesters β-TrCP away from IκBα, preventing IκBα ubiquitination and degradation; Ser-to-Ala mutation in the motif abolishes β-TrCP binding and NF-κB inhibition. Co-immunoprecipitation, mutagenesis, IκBα stability assay, NF-κB reporter assay, in vivo virulence model PLoS Pathogens High 23468625
2016 Rotavirus NSP1 induces β-TrCP degradation via hijacking a host Cullin-3–Rbx1 CRL complex at the Golgi; NSP1 co-localizes with Cul3–Rbx1 and targets β-TrCP for co-destruction at the proteasome; siRNA silencing of Cul3 or Rbx1 impairs NSP1-mediated β-TrCP degradation. Tandem-affinity purification coupled to mass spectrometry, siRNA knockdown, co-immunoprecipitation, subcellular localization imaging, proteasome inhibitor assay PLoS Pathogens High 27706223
2019 PARP11 mono-ADP-ribosylates β-TrCP, which promotes IFNAR1 ubiquitination and degradation by β-TrCP, thereby suppressing IFN-I antiviral signaling; PARP11 expression is upregulated by viral infection. Co-immunoprecipitation, ADP-ribosylation assay, IFNAR1 ubiquitination assay, siRNA, viral infection assay Nature Microbiology High 30988430
2018 TSPAN15 interacts specifically with BTRC/β-TrCP to promote ubiquitination and proteasomal degradation of phosphorylated IκBα, thereby triggering NF-κB nuclear translocation and transcription of metastasis-related genes. Co-immunoprecipitation, ubiquitination assay, NF-κB reporter assay, siRNA knockdown, cell migration/invasion assay Nature Communications High 29650964
2006 SCF(β-TrCP) promotes ubiquitination of pro-caspase-3; β-TrCP1 binds to the first 38 amino acids of pro-caspase-3; overexpression of β-TrCP1 shortens pro-caspase-3 half-life while dominant-negative β-TrCP1 extends it; SAG/ROC-SCF(β-TrCP) in vitro ubiquitination of pro-caspase-3 was demonstrated. Co-immunoprecipitation, in vitro ubiquitination assay, dominant-negative expression, siRNA, apoptosis assay Neoplasia High 17217622
2009 USP47 is a novel interactor of SCF(β-Trcp); both β-Trcp1 and β-Trcp2 bind specifically to USP47 through the WD-repeat region; USP47 depletion increases Cdc25A accumulation and decreases cell survival; USP47 does not behave as a canonical β-Trcp substrate (its levels are not affected by β-Trcp silencing). Co-immunoprecipitation, WD-repeat point mutations, siRNA, Cdc25A accumulation assay, cell viability assay Oncogene High 19966869
2011 βTrCP regulates BMI1 ubiquitination and proteasomal degradation; β-TrCP overexpression promotes BMI1 ubiquitination and degradation; a mutant BMI1 with an altered βTrCP recognition motif is more stable, interacts with βTrCP, and exhibits increased pro-oncogenic activity. Co-immunoprecipitation, ubiquitination assay, site-directed mutagenesis, siRNA knockdown Cell Cycle Medium 21430439
2012 USP37 interacts with βTrCP in a phosphorylation-dependent manner during G2; Plk1 kinase phosphorylates USP37 to enable βTrCP binding; βTrCP-mediated USP37 degradation at G2/M is required for mitotic entry; phosphorylation-site mutant USP37 resists Plk1-induced degradation and impairs G2/M transition. Co-immunoprecipitation, phospho-site mutagenesis, siRNA knockdown, cell cycle synchronization, Plk1 inhibition Journal of Biological Chemistry High 23027877
2018 β-TrCP and Casein Kinase II cooperate to degrade cyclin F at the G2/M transition; CKII phosphorylates a non-canonical TSGXXS motif on cyclin F; this β-TrCP-mediated degradation promotes mitotic progression and a mitotic transcriptional program. Co-immunoprecipitation, phosphorylation assay, mutagenesis, cell cycle synchronization, siRNA, transcriptional program analysis Cell Reports High 30257202
2017 β-TrCP targets DMRT1 for ubiquitylation and degradation, controlling the mitosis-to-meiosis transition in male germ cells; DMRT1 contains a consensus β-TrCP degron; conditional inactivation of β-TrCP2 in β-TrCP1-knockout male germ cells causes DMRT1 accumulation, failure to enter meiosis, and sterility; heterozygous deletion of Dmrt1 partially rescues meiosis in β-TrCP-deficient cells. Conditional knockout in mice, co-immunoprecipitation, ubiquitylation assay, genetic rescue (Dmrt1 heterozygous deletion) Development High 28982686
2015 βTRCP targets CReP (a PP1 specificity factor for eIF2α) for degradation upon DNA damage; stable CReP cannot be degraded, is required for full eIF2α phosphorylation after DNA damage, and maintains low translation during recovery. Ligase trapping ubiquitin substrate screen, stable CReP allele expression, eIF2α phosphorylation assay, translation assay PLoS Genetics High 26091241
2013 β-TrCP E3 ligase is the ubiquitin ligase for the mRNA decay factor AUF1; β-TrCP depletion stabilizes AUF1; overexpression enhances AUF1 ubiquitination and degradation; degradation requires phosphomimetic Hsp27 (p38-MK2 pathway) and phosphomimetic AUF1, linking MAP kinase signaling to AUF1 turnover. Co-immunoprecipitation, siRNA knockdown, ubiquitination assay, ARE-mRNA reporter assay Molecular and Cellular Biology Medium 23530064
2012 β-TrCP1 targets HuR for degradation in response to glycolysis inhibition; β-TrCP1 recognizes an unconventional motif (EEAMAIAS) on HuR phosphorylated by IKKα at Ser304; cytoplasmic translocation of HuR (via PKCα-mediated Ser318 phosphorylation) precedes β-TrCP1-mediated degradation. Co-immunoprecipitation, GST pulldown, site-directed mutagenesis, in vitro kinase assay, dominant-negative β-TrCP1, ubiquitination assay Journal of Biological Chemistry High 23115237
2019 ERAP1 binds the deubiquitylase USP47, displaces USP47-associated βTrCP, and promotes βTrCP degradation, thereby increasing Gli transcription factor levels and Hedgehog pathway activity; pharmacological inhibition of ERAP1 suppresses Hh-dependent tumor growth. Co-immunoprecipitation, pulldown, βTrCP degradation assay, Gli reporter assay, in vitro and in vivo tumor growth assay Nature Communications High 31341163
2016 SAG/RBX2–CUL5 complex ubiquitylates β-TrCP1 via atypical K11-linked ubiquitin chains using E2 enzymes UBCH10 and UBE2S; SAG and β-TrCP1 levels are inversely correlated; silencing UBCH10 or UBE2S (but not UBCH5C) causes β-TrCP1 accumulation. Co-immunoprecipitation, ubiquitin chain linkage analysis, siRNA, half-life assay Scientific Reports High 27910872
2018 S6K1 phosphorylates Mxi1 at Ser160, enabling β-Trcp to bind and promote Mxi1 ubiquitination and proteasomal degradation; a phosphorylation-deficient Mxi1-S160A mutant is more stable and more potent in suppressing Myc transcriptional activity and radioresistance. Tandem affinity purification/mass spectrometry, co-immunoprecipitation, in vitro kinase assay, in vivo ubiquitination assay, stable mutant expression Theranostics High 29507620
2019 β-TrCP1 and β-TrCP2 mutually target each other for ubiquitination and degradation in a degron-dependent manner; glucose deprivation activates AMPK to phosphorylate β-TrCP1, promoting its degradation by β-TrCP2 but not vice versa; β-TrCP2 preferentially degrades DEPTOR and REDD1 to activate mTORC1 and inhibit autophagy. Co-immunoprecipitation, ubiquitination assay, degron mutagenesis, AMPK inhibition/activation, autophagy assay, mTORC1 activity assay Cell Death and Differentiation High 31406304
2013 SCFβ-TRCP targets tumor suppressor MTSS1 for ubiquitination and proteasomal degradation; CKIδ phosphorylates Ser322 in the DSGXXS degron of MTSS1 to trigger β-TRCP binding; non-degradable MTSS1-S322A more potently inhibits breast and prostate cancer cell proliferation and migration. Co-immunoprecipitation, in vitro kinase assay, ubiquitination assay, siRNA, cell proliferation/migration assay Oncotarget High 24318128
2021 β-Trcp is the E3 ubiquitin ligase for LZTS2; CK1δ phosphorylates LZTS2 to enable β-Trcp recognition; β-Trcp/CK1δ-mediated LZTS2 degradation activates PI3K/AKT signaling and promotes hepatocellular carcinoma progression and metastasis. Co-immunoprecipitation, in vitro kinase assay, ubiquitination assay, siRNA, in vitro/in vivo tumor models Oncogene High 33420362
2018 USP24 deubiquitinase stabilizes β-TrCP protein (as well as p300), leading to increased NF-κB levels and decreased IκB, which drives IL-6 transcription in macrophages and cancer cells to promote cancer malignancy. Co-immunoprecipitation, siRNA knockdown, protein stability assay, IL-6 expression assay Nature Communications Medium 30266897
2007 RASSF1C (but not RASSF1A) interacts with βTrCP through SS18-GYXS19 residues and promotes β-catenin accumulation by inhibiting βTrCP-mediated β-catenin degradation; RASSF1C binding to βTrCP does not involve the canonical WD40 substrate-binding domain. Co-immunoprecipitation, siRNA knockdown, β-catenin stability assay, mutagenesis Cancer Research Medium 17283138
2005 FGD1 (Cdc42 GEF) is degraded by SCF(FWD1/β-TrCP) upon phosphorylation of serines in a DSGIDS motif; a phosphorylation-deficient FGD1-SA mutant is more stable, has increased Cdc42-GEF activity, and exhibits higher cell motility. Co-immunoprecipitation, site-directed mutagenesis, protein stability assay, Cdc42-GTP assay, cell motility assay Genes to Cells High 15743413
2018 STIL is a substrate of SCF-βTrCP; the βTrCP binding depends on a DSG motif in STIL, with Ser395 phosphorylated in vivo; SCFβTrCP-mediated STIL degradation occurs throughout interphase; CDK2 activity protects STIL from βTrCP-mediated degradation; mutation of the DSG motif causes massive centrosome amplification. Proteomics with MLN4924, co-immunoprecipitation, phospho-site mutagenesis, CDK2 inhibition, centrosome counting Open Biology High 29445034
2008 STAT1 phosphorylated by ERK at Ser727 is targeted for proteasomal degradation by SCF(βTRCP); βTRCP binds wild-type STAT1 but not the non-phosphorylatable STAT1-S727A mutant; βTRCP silencing or ERK pharmacological inhibition stabilizes STAT1. Co-immunoprecipitation, site-directed mutagenesis (S727A), siRNA, ERK inhibitor, proteasomal degradation assay Journal of Biological Chemistry Medium 18378670
2006 Pin1 stabilizes Emi1 during G2 by preventing its association with SCF(βTrCP) in an isomerization-dependent manner; Pin1 binds Emi1 in G2 cells to shield it from βTrCP-mediated destruction, despite concurrent activity of Plx1 and cyclin A/CDK. Co-immunoprecipitation, Pin1 isomerase assay, cell cycle synchronization, Emi1 stability assay, Xenopus XL2 cell analysis EMBO Reports Medium 17159919
2021 βTrCP is the E3 ligase for TFRC (transferrin receptor) ubiquitination; TRIB2 associates with βTrCP to reduce labile iron, thereby desensitizing liver cancer cells to ferroptosis; βTrCP knockout abolishes TRIB2's ability to reduce labile iron. Co-immunoprecipitation, ubiquitination assay, βTrCP knockout, ferroptosis assay, labile iron pool measurement Cell Death Discovery Medium 34315867
2019 p38 MAPK phosphorylates Snail at Ser107, which suppresses DYRK2-mediated Ser104 phosphorylation required for GSK3β-dependent Snail phosphorylation and βTrCP-mediated Snail ubiquitination and degradation, thereby stabilizing Snail and promoting EMT. In vitro kinase assay (p38, DYRK2, GSK3β), co-immunoprecipitation, ubiquitination assay, site-directed mutagenesis, cell migration assay Cancer Research High 31209060
2017 PLK1 is ubiquitinated by SCFβTrCP and degraded by the proteasome when HSP90 is inhibited; CDK1 is the major kinase mediating this β-TrCP-dependent PLK1 destruction; this pathway arrests cell cycle at G1/S by preventing CDH1 degradation. Co-immunoprecipitation, CDK1 inhibition, geldanamycin treatment, cell cycle synchronization, proteasome inhibitor rescue FASEB Journal Medium 28360195

Source papers

Stage 0 corpus · 100 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2008 Deregulated proteolysis by the F-box proteins SKP2 and beta-TrCP: tipping the scales of cancer. Nature reviews. Cancer 810 18500245
2006 S6K1- and betaTRCP-mediated degradation of PDCD4 promotes protein translation and cell growth. Science (New York, N.Y.) 606 17053147
2003 Structure of a beta-TrCP1-Skp1-beta-catenin complex: destruction motif binding and lysine specificity of the SCF(beta-TrCP1) ubiquitin ligase. Molecular cell 557 12820959
2012 Nrf2 is controlled by two distinct β-TrCP recognition motifs in its Neh6 domain, one of which can be modulated by GSK-3 activity. Oncogene 550 22964642
1999 An F-box protein, FWD1, mediates ubiquitin-dependent proteolysis of beta-catenin. The EMBO journal 480 10228155
2003 Degradation of Cdc25A by beta-TrCP during S phase and in response to DNA damage. Nature 380 14603323
1999 beta-Trcp couples beta-catenin phosphorylation-degradation and regulates Xenopus axis formation. Proceedings of the National Academy of Sciences of the United States of America 352 10339577
2007 Degradation of Mcl-1 by beta-TrCP mediates glycogen synthase kinase 3-induced tumor suppression and chemosensitization. Molecular and cellular biology 334 17387146
2003 Control of meiotic and mitotic progression by the F box protein beta-Trcp1 in vivo. Developmental cell 327 12791266
2003 Prophase destruction of Emi1 by the SCF(betaTrCP/Slimb) ubiquitin ligase activates the anaphase promoting complex to allow progression beyond prometaphase. Developmental cell 301 12791267
2009 Vpu antagonizes BST-2-mediated restriction of HIV-1 release via beta-TrCP and endo-lysosomal trafficking. PLoS pathogens 289 19478868
2004 The many faces of beta-TrCP E3 ubiquitin ligases: reflections in the magic mirror of cancer. Oncogene 283 15021890
2011 DEPTOR, an mTOR inhibitor, is a physiological substrate of SCF(βTrCP) E3 ubiquitin ligase and regulates survival and autophagy. Molecular cell 245 22017876
2001 ATF4 degradation relies on a phosphorylation-dependent interaction with the SCF(betaTrCP) ubiquitin ligase. Molecular and cellular biology 225 11238952
2011 mTOR drives its own activation via SCF(βTrCP)-dependent degradation of the mTOR inhibitor DEPTOR. Molecular cell 216 22017875
1999 Ubiquitin-dependent degradation of IkappaBalpha is mediated by a ubiquitin ligase Skp1/Cul 1/F-box protein FWD1. Proceedings of the National Academy of Sciences of the United States of America 188 10097128
2011 mTOR generates an auto-amplification loop by triggering the βTrCP- and CK1α-dependent degradation of DEPTOR. Molecular cell 181 22017877
2010 Plk4 trans-autophosphorylation regulates centriole number by controlling betaTrCP-mediated degradation. Journal of cell science 176 20516151
2009 betaTrCP- and Rsk1/2-mediated degradation of BimEL inhibits apoptosis. Molecular cell 163 19150432
2015 Dual regulation of transcription factor Nrf2 by Keap1 and by the combined actions of β-TrCP and GSK-3. Biochemical Society transactions 160 26551701
2003 FWD1-mediated degradation of FREQUENCY in Neurospora establishes a conserved mechanism for circadian clock regulation. The EMBO journal 149 12941694
2007 Beta-TrCP1-mediated degradation of PERIOD2 is essential for circadian dynamics. Journal of biological rhythms 144 17876059
2009 Rotavirus NSP1 inhibits NFkappaB activation by inducing proteasome-dependent degradation of beta-TrCP: a novel mechanism of IFN antagonism. PLoS pathogens 137 19180189
2008 Plk1 regulates mitotic Aurora A function through betaTrCP-dependent degradation of hBora. Chromosoma 130 18521620
2009 Phosphorylation of p53 by IkappaB kinase 2 promotes its degradation by beta-TrCP. Proceedings of the National Academy of Sciences of the United States of America 129 19196987
2006 Gli2 is targeted for ubiquitination and degradation by beta-TrCP ubiquitin ligase. The Journal of biological chemistry 121 16651270
1999 Inducible degradation of IkappaBalpha by the proteasome requires interaction with the F-box protein h-betaTrCP. The Journal of biological chemistry 117 10075690
2003 betaTrCP-mediated proteolysis of NF-kappaB1 p105 requires phosphorylation of p105 serines 927 and 932. Molecular and cellular biology 116 12482991
2005 Beta-TrCP recognizes a previously undescribed nonphosphorylated destruction motif in Cdc25A and Cdc25B phosphatases. Proceedings of the National Academy of Sciences of the United States of America 113 15845771
2015 EBV-miR-BART10-3p facilitates epithelial-mesenchymal transition and promotes metastasis of nasopharyngeal carcinoma by targeting BTRC. Oncotarget 100 26497204
2012 The Fbw7 and betaTRCP E3 ubiquitin ligases and their roles in tumorigenesis. Frontiers in bioscience (Landmark edition) 100 22652772
2018 USP24 induces IL-6 in tumor-associated microenvironment by stabilizing p300 and β-TrCP and promotes cancer malignancy. Nature communications 98 30266897
2003 Impaired degradation of inhibitory subunit of NF-kappa B (I kappa B) and beta-catenin as a result of targeted disruption of the beta-TrCP1 gene. Proceedings of the National Academy of Sciences of the United States of America 97 12843402
2013 Poxvirus targeting of E3 ligase β-TrCP by molecular mimicry: a mechanism to inhibit NF-κB activation and promote immune evasion and virulence. PLoS pathogens 96 23468625
2005 Wnt, hedgehog and snail: sister pathways that control by GSK-3beta and beta-Trcp in the regulation of metastasis. Cell cycle (Georgetown, Tex.) 96 15917668
2002 Molecular genetic analysis of malignant melanomas for aberrations of the WNT signaling pathway genes CTNNB1, APC, ICAT and BTRC. International journal of cancer 94 12124804
2019 ADP-ribosyltransferase PARP11 modulates the interferon antiviral response by mono-ADP-ribosylating the ubiquitin E3 ligase β-TrCP. Nature microbiology 88 30988430
2011 Dual regulation of the transcriptional activity of Nrf1 by β-TrCP- and Hrd1-dependent degradation mechanisms. Molecular and cellular biology 87 21911472
2005 beta-TrCP binding and processing of NF-kappaB2/p100 involve its phosphorylation at serines 866 and 870. Cellular signalling 87 16303288
2004 Smad4 protein stability is regulated by ubiquitin ligase SCF beta-TrCP1. The Journal of biological chemistry 87 14988407
2014 KRAS protein stability is regulated through SMURF2: UBCH5 complex-mediated β-TrCP1 degradation. Neoplasia (New York, N.Y.) 86 24709419
2006 Oncogenic BRAF regulates beta-Trcp expression and NF-kappaB activity in human melanoma cells. Oncogene 85 17001349
2006 SAG/ROC-SCF beta-TrCP E3 ubiquitin ligase promotes pro-caspase-3 degradation as a mechanism of apoptosis protection. Neoplasia (New York, N.Y.) 81 17217622
2018 TSPAN15 interacts with BTRC to promote oesophageal squamous cell carcinoma metastasis via activating NF-κB signaling. Nature communications 77 29650964
1999 Common pathway for the ubiquitination of IkappaBalpha, IkappaBbeta, and IkappaBepsilon mediated by the F-box protein FWD1. The Journal of biological chemistry 75 10497169
2019 Inhibition of mTOR complex 1/p70 S6 kinase signaling elevates PD-L1 levels in human cancer cells through enhancing protein stabilization accompanied with enhanced β-TrCP degradation. Oncogene 71 31316145
2009 The ubiquitin-specific protease USP47 is a novel beta-TRCP interactor regulating cell survival. Oncogene 69 19966869
2008 The role of {beta}-TrCP1 and {beta}-TrCP2 in circadian rhythm generation by mediating degradation of clock protein PER2. Journal of biochemistry 65 18782782
2013 The E3 ubiquitin ligases β-TrCP and FBXW7 cooperatively mediates GSK3-dependent Mcl-1 degradation induced by the Akt inhibitor API-1, resulting in apoptosis. Molecular cancer 64 24261825
2016 Comparative Proteomics Reveals Strain-Specific β-TrCP Degradation via Rotavirus NSP1 Hijacking a Host Cullin-3-Rbx1 Complex. PLoS pathogens 58 27706223
2020 The characteristics and roles of β-TrCP1/2 in carcinogenesis. The FEBS journal 56 33021036
2007 The ubiquitin ligase SCF(betaTrCP) regulates the degradation of the growth hormone receptor. The Journal of biological chemistry 54 17500058
2012 Erioflorin stabilizes the tumor suppressor Pdcd4 by inhibiting its interaction with the E3-ligase β-TrCP1. PloS one 53 23056346
2005 SCF(beta-TrCP1) controls Smad4 protein stability in pancreatic cancer cells. The American journal of pathology 51 15855639
2014 TRIB2 inhibits Wnt/β-Catenin/TCF4 signaling through its associated ubiquitin E3 ligases, β-TrCP, COP1 and Smurf1, in liver cancer cells. FEBS letters 50 25311538
2012 The mRNA-stabilizing factor HuR protein is targeted by β-TrCP protein for degradation in response to glycolysis inhibition. The Journal of biological chemistry 50 23115237
2021 TRIB2 desensitizes ferroptosis via βTrCP-mediated TFRC ubiquitiantion in liver cancer cells. Cell death discovery 49 34315867
2019 ERAP1 promotes Hedgehog-dependent tumorigenesis by controlling USP47-mediated degradation of βTrCP. Nature communications 49 31341163
2015 Putative E3 ubiquitin ligase of human rotavirus inhibits NF-κB activation by using molecular mimicry to target β-TrCP. mBio 48 25626907
2007 Somatic mutations of the beta-TrCP gene in gastric cancer. APMIS : acta pathologica, microbiologica, et immunologica Scandinavica 48 17295679
2009 An insertion/deletion polymorphism in the 3' untranslated region of beta-transducin repeat-containing protein (betaTrCP) is associated with susceptibility for hepatocellular carcinoma in Chinese. Biochemical and biophysical research communications 47 19931512
2007 Regulated degradation of the HIV-1 Vpu protein through a betaTrCP-independent pathway limits the release of viral particles. PLoS pathogens 47 17676996
2011 βTrCP regulates BMI1 protein turnover via ubiquitination and degradation. Cell cycle (Georgetown, Tex.) 46 21430439
2008 Novel insights into FGD3, a putative GEF for Cdc42, that undergoes SCF(FWD1/beta-TrCP)-mediated proteasomal degradation analogous to that of its homologue FGD1 but regulates cell morphology and motility differently from FGD1. Genes to cells : devoted to molecular & cellular mechanisms 46 18363964
2007 RASSF1C, an isoform of the tumor suppressor RASSF1A, promotes the accumulation of beta-catenin by interacting with betaTrCP. Cancer research 46 17283138
2008 ERK and the F-box protein betaTRCP target STAT1 for degradation. The Journal of biological chemistry 45 18378670
2006 Pin1 stabilizes Emi1 during G2 phase by preventing its association with SCF(betatrcp). EMBO reports 45 17159919
2019 p38 Stabilizes Snail by Suppressing DYRK2-Mediated Phosphorylation That Is Required for GSK3β-βTrCP-Induced Snail Degradation. Cancer research 44 31209060
2008 Epigenetic silencing of AXIN2/betaTrCP and deregulation of p53-mediated control lead to wild-type beta-catenin nuclear accumulation in lung tumorigenesis. Oncogene 43 18372914
2019 The cross talk of two family members of β-TrCP in the regulation of cell autophagy and growth. Cell death and differentiation 42 31406304
2013 SCF β-TRCP targets MTSS1 for ubiquitination-mediated destruction to regulate cancer cell proliferation and migration. Oncotarget 42 24318128
2012 Skp1-Cul1-F-box ubiquitin ligase (SCF(βTrCP))-mediated destruction of the ubiquitin-specific protease USP37 during G2-phase promotes mitotic entry. The Journal of biological chemistry 41 23027877
2005 Overexpression of human beta TrCP1 deleted of its F box induces tumorigenesis in transgenic mice. Oncogene 41 15735746
2003 NMR studies of the phosphorylation motif of the HIV-1 protein Vpu bound to the F-box protein beta-TrCP. Biochemistry 41 14674748
2017 β-TrCP1 Is a Vacillatory Regulator of Wnt Signaling. Cell chemical biology 40 28736239
2010 beta-TrCP inhibition reduces prostate cancer cell growth via upregulation of the aryl hydrocarbon receptor. PloS one 39 20140206
2020 The circular RNA FAM169A functions as a competitive endogenous RNA and regulates intervertebral disc degeneration by targeting miR-583 and BTRC. Cell death & disease 38 32366862
1999 Molecular dissection of the interactions among IkappaBalpha, FWD1, and Skp1 required for ubiquitin-mediated proteolysis of IkappaBalpha. The Journal of biological chemistry 37 10514433
2022 TRIM67 Suppresses TNFalpha-Triggered NF-kB Activation by Competitively Binding Beta-TrCP to IkBa. Frontiers in immunology 36 35273593
2018 S6K1 phosphorylation-dependent degradation of Mxi1 by β-Trcp ubiquitin ligase promotes Myc activation and radioresistance in lung cancer. Theranostics 36 29507620
2016 SAG/RBX2 E3 ligase complexes with UBCH10 and UBE2S E2s to ubiquitylate β-TrCP1 via K11-linkage for degradation. Scientific reports 36 27910872
2015 CD166 positively regulates MCAM via inhibition to ubiquitin E3 ligases Smurf1 and βTrCP through PI3K/AKT and c-Raf/MEK/ERK signaling in Bel-7402 hepatocellular carcinoma cells. Cellular signalling 35 26004137
2018 β-TrCP- and Casein Kinase II-Mediated Degradation of Cyclin F Controls Timely Mitotic Progression. Cell reports 33 30257202
2015 Erbin is a novel substrate of the Sag-βTrCP E3 ligase that regulates KrasG12D-induced skin tumorigenesis. The Journal of cell biology 33 26056141
2005 Regulation of lung cancer cell growth and invasiveness by beta-TRCP. Molecular carcinogenesis 32 15536641
2015 DNA Damage Regulates Translation through β-TRCP Targeting of CReP. PLoS genetics 30 26091241
2013 Hsp27 and F-box protein β-TrCP promote degradation of mRNA decay factor AUF1. Molecular and cellular biology 28 23530064
2023 The novel β-TrCP protein isoform hidden in circular RNA confers trastuzumab resistance in HER2-positive breast cancer. Redox biology 27 37783059
2004 Hierarchical order of phosphorylation events commits Cdc25A to betaTrCP-dependent degradation. Cell cycle (Georgetown, Tex.) 27 14752276
2021 β-Trcp and CK1δ-mediated degradation of LZTS2 activates PI3K/AKT signaling to drive tumorigenesis and metastasis in hepatocellular carcinoma. Oncogene 26 33420362
2017 Regulation of mitosis-meiosis transition by the ubiquitin ligase β-TrCP in male germ cells. Development (Cambridge, England) 26 28982686
2008 Multiple isoforms of beta-TrCP display differential activities in the regulation of Wnt signaling. Cellular signalling 26 18929646
2016 Increased βTrCP are associated with imiquimod-induced psoriasis-like skin inflammation in mice via NF-κB signaling pathway. Gene 25 27476970
2022 An inhibitor of interaction between the transcription factor NRF2 and the E3 ubiquitin ligase adapter β-TrCP delivers anti-inflammatory responses in mouse liver. Redox biology 24 35839629
2019 An E3 ubiquitin ligase TRIM9 is involved in WSSV infection via interaction with β-TrCP. Developmental and comparative immunology 23 30910419
2017 G1/S phase progression is regulated by PLK1 degradation through the CDK1/βTrCP axis. FASEB journal : official publication of the Federation of American Societies for Experimental Biology 23 28360195
2005 The FWD1/beta-TrCP-mediated degradation pathway establishes a 'turning off switch' of a Cdc42 guanine nucleotide exchange factor, FGD1. Genes to cells : devoted to molecular & cellular mechanisms 23 15743413
2021 WBP2 promotes BTRC mRNA stability to drive migration and invasion in triple-negative breast cancer via NF-κB activation. Molecular oncology 21 34197030
2018 The SKP1-Cullin-F-box E3 ligase βTrCP and CDK2 cooperate to control STIL abundance and centriole number. Open biology 21 29445034
2015 β-TrCP1 degradation is a novel action mechanism of PI3K/mTOR inhibitors in triple-negative breast cancer cells. Experimental & molecular medicine 21 25721419