Affinage

APBB1

Amyloid beta precursor protein binding family B member 1 · UniProt O00213

Length
710 aa
Mass
77.2 kDa
Annotated
2026-06-09
100 papers in source corpus 57 papers cited in narrative 57 extracted findings
Cross-family judge vs UniProt: Affinage preferred faithfulness: 8/8 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

APBB1/Fe65 is a multidomain neuronal adaptor protein that couples the amyloid precursor protein (APP) to membrane trafficking, the actin cytoskeleton, and nuclear gene regulation, thereby integrating APP signaling with cortical development, neurite outgrowth, and the genotoxic stress response (PMID:8537337, PMID:11441186, PMID:16407979). Its two phosphotyrosine-binding (PTB) domains and an N-terminal WW domain create a bridging scaffold: the C-terminal PTB2 domain binds the YENPTY/NPxY motif of the APP intracellular domain in a phosphorylation-independent manner (PMID:8537337, PMID:8887653, PMID:18833287), the N-terminal PTB1 domain engages the lipoprotein receptors LRP1 and ApoEr2 to assemble trimeric receptor–Fe65–APP complexes (PMID:15115822, PMID:16638748, PMID:21968187), and the WW domain binds the proline-rich actin regulator Mena through an induced-fit mechanism (PMID:9407065, PMID:17686488). Through these interactions Fe65 promotes APP cell-surface delivery and modulates secretase processing, increasing sAPPα and Aβ secretion while shifting the balance of APP C-terminal fragments (PMID:10075692, PMID:17170108), and it stabilizes the γ-secretase-released AICD to permit its nuclear entry (PMID:11544248, PMID:12358789). In the nucleus Fe65 nucleates a transcriptionally active AICD–Fe65–Tip60 histone acetyltransferase complex that, together with the nucleosome assembly factor SET, drives target gene transcription (PMID:11441186, PMID:12563035, PMID:15592452), whereas recruitment of Teashirt/HDAC converts it into a gene-silencing complex (PMID:19343227). Fe65 is essential for the DNA damage response, recruiting the Tip60–TRRAP complex to double-strand breaks and promoting histone H4 acetylation and repair in an APP-dependent manner (PMID:17121854, PMID:19282473). At the cell periphery Fe65 drives Rac1-dependent neurite outgrowth by activating ARF6 and relieving ELMO1 autoinhibition within an ELMO1–DOCK180 module (PMID:24056087, PMID:29615491, PMID:33047393). Its activities are gated by phosphorylation: APP Thr668 and Tyr682 phosphorylation disrupt Fe65–APP binding (PMID:11517218, PMID:18833287, PMID:19221419), c-Abl phosphorylation of Fe65 Tyr547 stimulates transcription (PMID:15031292), and SGK1 phosphorylation of Fe65 Ser610 attenuates APP binding and amyloidogenic processing (PMID:26188042). Fe65 is required for cortical lamination and basement membrane assembly downstream of the APP family, with knockout mice showing cortical dysplasia phenocopying APP/APLP triple knockouts (PMID:16407979, PMID:18278038).

Mechanistic history

Synthesis pass · year-by-year structured walk · 22 steps
  1. 1995 High

    Established that Fe65 is a direct APP-binding adaptor, identifying the molecular interaction that anchors all subsequent models.

    Evidence GST pulldown and yeast two-hybrid against the APP intracellular domain centered on the NPTY sequence

    PMID:8537337

    Open questions at the time
    • Which of the two PTB domains is responsible was not resolved here
    • Functional consequence of the interaction unaddressed
  2. 1996 High

    Mapped the APP interaction to Fe65 PTB2 and the YENPTY motif and distinguished it from X11 binding, defining domain specificity.

    Evidence Site-directed mutagenesis of YENPTY with binding readouts

    PMID:8887653

    Open questions at the time
    • Phosphorylation regulation of binding not yet examined
    • Structural basis unknown
  3. 1997 High

    Showed Fe65 is a tripartite scaffold by identifying the WW domain partner Mena, linking Fe65 to the actin cytoskeleton beyond APP.

    Evidence Expression library screen, SPOTS peptide synthesis, co-IP from COS cells and brain affinity purification

    PMID:9407065

    Open questions at the time
    • Cellular consequence of the Mena link not yet defined
    • Whether APP and Mena bind simultaneously untested
  4. 1998 High

    Revealed a nuclear function by identifying the transcription factor CP2/LSF as a PID1 partner and showing Fe65 partitions between nucleus and cytoplasm.

    Evidence Yeast interaction trap, co-IP, subcellular fractionation, deletion mutagenesis

    PMID:9685356

    Open questions at the time
    • Transcriptional output of the CP2/LSF interaction not yet measured
    • Signal controlling nuclear entry unknown
  5. 1999 High

    Linked Fe65 to APP trafficking and processing, showing it increases APP surface delivery and secretase product release.

    Evidence Immunofluorescence co-localization, cell-surface biotinylation, sAPPα/Aβ ELISA

    PMID:10075692

    Open questions at the time
    • Direction of effect (pro- vs anti-amyloidogenic) later found context-dependent
    • Mechanism of surface enhancement unresolved
  6. 2000 High

    Defined APP as a cytosolic anchor that retains Fe65, establishing how membrane APP controls Fe65 nuclear access.

    Evidence GFP-Fe65 imaging, deletion mutagenesis, nuclear fractionation in COS7 and PC12 cells

    PMID:11085987

    Open questions at the time
    • Trigger releasing Fe65 from the anchor not yet identified
    • Role of the WW domain in translocation mechanistically unexplained
  7. 2001 High

    Defined the central nuclear effector module: AICD-Fe65-Tip60 complex acts as a potent transcriptional activator, providing the gamma-secretase signaling endpoint.

    Evidence Co-IP and Gal4/LexA transcription reporter assays

    PMID:11441186

    Open questions at the time
    • Endogenous target genes not identified here
    • Relative contribution of AICD vs Fe65 to activation unresolved
  8. 2001 High

    Showed Fe65 stabilizes the otherwise labile AICD, explaining how the cleavage product survives to reach the nucleus.

    Evidence AICD transfection, co-IP, subcellular microscopy

    PMID:11544248

    Open questions at the time
    • Mechanism of stabilization (degradation pathway blocked) unclear
    • Whether Fe65 accompanies AICD into the nucleus debated in later work
  9. 2001 High

    Connected Fe65 to cell motility and the lipoprotein receptor LRP, assembling the trimeric LRP-Fe65-APP complex that governs APP processing.

    Evidence Migration assay, co-IP, GST pulldown, RNAi epistasis, FRET

    PMID:11425871 PMID:11606623 PMID:15115822

    Open questions at the time
    • How receptor occupancy is sensed not defined
    • Quantitative stoichiometry of the trimeric complex unknown
  10. 2002 High

    Identified phosphorylation of APP Thr668 as a conformational switch that releases Fe65 and showed Fe65 nuclear function controls cell-cycle gene expression.

    Evidence Mutagenesis, co-IP, Aβ ELISA, cell-cycle/reporter/thymidine rescue assays; γ-secretase product nuclear imaging with FRET

    PMID:11517218 PMID:12089154 PMID:12358789

    Open questions at the time
    • Kinase responsible for Thr668 phosphorylation not pinned down here
    • In vivo relevance of cell-cycle block unestablished
  11. 2002 High

    Demonstrated in vivo pathway conservation: C. elegans feh-1 and apl-1 act together to control pharyngeal pumping and viability.

    Evidence Deletion mutants, RNAi, genetic epistasis, binding assay, immunostaining

    PMID:11896189

    Open questions at the time
    • Mammalian physiological correlate of pharyngeal phenotype unclear
    • Downstream effectors in worm not defined
  12. 2003 Medium

    Refined the transcriptional mechanism (Tip60-dependence distinct from JIP-1) and extended ICD stabilization to APLP1/APLP2, broadening Fe65's regulatory scope.

    Evidence Reporter assays with Tip60 inhibition, biochemical fractionation, co-transfection; growth-cone localization and ERK1/2 phosphosite mapping

    PMID:12563035 PMID:12779321 PMID:12843239 PMID:14697653

    Open questions at the time
    • Functional consequence of ERK1/2 phosphorylation untested
    • Specificity of ICD stabilization across family members partial
  13. 2004 High

    Identified c-Abl phosphorylation of Fe65 Tyr547 as an activating signal and uncovered competitive (Alcadein) and worm gene-expression links, showing the nuclear complex is tunable.

    Evidence In vitro kinase assay, mutagenesis, reporter assays, competition co-IP, C. elegans mutant analysis

    PMID:15031292 PMID:15037614 PMID:15355315

    Open questions at the time
    • Upstream signals activating c-Abl toward Fe65 unknown
    • Endogenous targets of competitive ICD regulation limited
  14. 2005 High

    Expanded the chromatin machinery (SET) and revealed additional partners (Tau, P2X2, 14-3-3γ) plus an autoproteolytic high-affinity fragment, diversifying Fe65 functions and species-specific regulation.

    Evidence ChIP, RNAi, reporter assays, co-IP, immunogold EM, electrophysiology, cleavage/secretion assays

    PMID:15592452 PMID:15647266 PMID:15686969 PMID:16223726 PMID:16330549 PMID:16332686

    Open questions at the time
    • Physiological role of p65FE65 cleavage fragment unclear
    • Whether Fe65 or APP is the dominant transactivator context-dependent
  15. 2006 High

    Established Fe65's essential roles in the DNA damage response and in cortical development, placing it downstream of APP-family signaling in vivo.

    Evidence Fe65 KO and Fe65/Fe65L1 dKO mice, genotoxic survival assays, γH2AX/p53 readouts, histology, laminin assays, genetic epistasis with APP family KO; ApoEr2 binding and processing assays

    PMID:16407979 PMID:16638748 PMID:16716194 PMID:17121854 PMID:17170108

    Open questions at the time
    • Molecular link between Fe65 and DSB repair machinery not yet defined here
    • Whether developmental and DNA-repair roles share a mechanism unknown
  16. 2007 High

    Provided structural insight into WW–Mena binding, defined Fe65 as a negative regulator of axon branching, and showed it stimulates γ-secretase AICD liberation.

    Evidence X-ray crystallography of WW domain, hippocampal neuron morphometry with interaction-deficient mutants, APP processing/ELISA assays

    PMID:17383198 PMID:17686488 PMID:17855370

    Open questions at the time
    • Mechanism by which Fe65 stimulates γ-secretase not structurally defined
    • WW-domain ligand mediating axon-branching effect not identified
  17. 2008 High

    Resolved the AICD-Fe65 binding interface crystallographically and identified the extracellular ligand TAG1 and regulators (Dexras1, stress kinase) governing Fe65 nuclear signaling.

    Evidence X-ray crystallography, ITC, NMR, mutagenesis; KO models with BrdU tracing; co-IP and reporter assays; stress/fractionation experiments

    PMID:18278038 PMID:18468999 PMID:18833287 PMID:18922798

    Open questions at the time
    • How extracellular TAG1 signaling is transduced to γ-secretase incompletely defined
    • Identity of the stress-activated kinase phosphorylating APP not specified
  18. 2009 High

    Defined the molecular DNA-repair mechanism (Tip60-TRRAP recruitment and H4 acetylation) and an HDAC-dependent gene-silencing complex (Teashirt/SET), plus a second APP Tyr682 regulatory switch.

    Evidence ChIP, knockdown, H4 acetylation and DNA repair assays, mutagenesis; yeast two-hybrid, reporter, co-IP; phospho-mutant binding assays

    PMID:19221419 PMID:19282473 PMID:19343227

    Open questions at the time
    • How Fe65 senses DNA breaks to target Tip60-TRRAP unknown
    • Balance between activating and silencing complexes not determined
  19. 2012 Medium

    Extended Fe65 interactions to disease-relevant proteins (huntingtin, Stathmin1 regulation), implicating it in proteostasis and cytoskeletal gene control.

    Evidence Co-IP, knockdown, ubiquitination and proteasome assays; quantitative proteomics with KO validation

    PMID:22352297 PMID:22902274

    Open questions at the time
    • Single-lab findings without independent replication
    • Physiological significance of mutant Htt stabilization unclear
  20. 2013 High

    Identified the ARF6-Rac1 neurite-outgrowth pathway and additional partners (PP1γ, SV2A/SERCA2, BLM), linking Fe65 to cytoskeletal dynamics, calcium homeostasis, and replication.

    Evidence Co-IP, GTPase activation, neurite outgrowth, KO proteomics, thapsigargin sensitivity, live-cell imaging

    PMID:23531501 PMID:23572515 PMID:24056087 PMID:24284412

    Open questions at the time
    • Mechanistic integration of calcium/replication roles with core APP axis unclear
    • PP1γ and BLM findings are single-lab
  21. 2015 High

    Identified SGK1-mediated Fe65 Ser610 phosphorylation as a regulator of amyloidogenic processing and a Tip60/cortactin acetylation pathway controlling cancer cell migration, broadening Fe65 regulation and roles.

    Evidence In vitro kinase assay, mutagenesis, co-IP, APP processing and proteasome assays; migration/invasion and acetylation assays

    PMID:26166158 PMID:26188042

    Open questions at the time
    • Upstream signals activating SGK1 toward Fe65 unknown
    • Cortactin acetylation role outside breast cancer untested
  22. 2020 High

    Mechanistically resolved the neurite-outgrowth pathway, showing Fe65 relieves ELMO1 autoinhibition and routes ELMO1 through recycling endosomes to the plasma membrane to activate Rac1 via ARF6-ELMO1-DOCK180.

    Evidence Co-IP, ELMO1 autoinhibition and Rac1 activation assays, membrane/recycling-endosome fractionation, neurite outgrowth, KO cells

    PMID:29615491 PMID:33047393

    Open questions at the time
    • How this cytoplasmic role is coordinated with nuclear signaling unknown
    • In vivo neuronal requirement not established

Open questions

Synthesis pass · forward-looking unresolved questions
  • It remains unresolved how Fe65's distinct activities — APP trafficking/processing, AICD-Tip60 transcription, DNA-damage repair, and ARF6-Rac1 cytoskeletal signaling — are spatiotemporally coordinated within a single cell, and whether a unifying upstream signal switches Fe65 between these modes.
  • No integrated model linking cytoplasmic and nuclear pools
  • Physiological stimuli partitioning Fe65 among functions undefined
  • No human disease-causing mutation reported in this corpus

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0060090 molecular adaptor activity 4 GO:0140110 transcription regulator activity 4 GO:0008092 cytoskeletal protein binding 3 GO:0098772 molecular function regulator activity 3
Localization
GO:0005634 nucleus 4 GO:0005886 plasma membrane 3 GO:0000228 nuclear chromosome 2 GO:0005829 cytosol 2 GO:0005856 cytoskeleton 2 GO:0005783 endoplasmic reticulum 1
Pathway
R-HSA-392499 Metabolism of proteins 4 R-HSA-74160 Gene expression (Transcription) 4 R-HSA-162582 Signal Transduction 3 R-HSA-9609507 Protein localization 3 R-HSA-1266738 Developmental Biology 2 R-HSA-73894 DNA Repair 2
Partners
APPARF6CP2/LSFELMO1LRP1MENASETTIP60
Complex memberships
AICD-Fe65-Tip60 transcription complexFe65-ELMO1-DOCK180 complexFe65-SET-Teashirt silencing complexLRP-Fe65-APP trimeric complex

Evidence

Reading pass · 57 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
1995 The two PID/PTB domains of Fe65 bind to the intracellular domain of APP (centered on the NPTY sequence), as demonstrated by GST fusion protein co-precipitation and yeast two-hybrid screening of a human brain cDNA library. GST pulldown, yeast two-hybrid The Journal of biological chemistry High 8537337
1996 The second PTB/PI domain of FE65 binds the YENPTY motif in the intracellular domain of APP in a phosphorylation-independent manner, and the FE65 binding site differs from that of X11 as shown by differential effects of YENPTY mutations. Site-directed mutagenesis, binding assays Molecular and cellular biology High 8887653
1997 The WW domain of FE65 binds proline-rich sequences containing a PPLP core motif in Mena (mammalian enabled), and this interaction occurs in vivo as demonstrated by co-immunoprecipitation from COS cell extracts. Expression library screen, SPOTS peptide synthesis, co-immunoprecipitation, affinity purification from mouse brain The Journal of biological chemistry High 9407065
1997 Fe65 interacts in vivo with APP in mammalian cells (co-immunoprecipitation), and this interaction differs from Shc/IRS-1 PTB domain interactions: it is phosphorylation-independent, requires a larger APP intracellular region, and mutant APP linked to familial Alzheimer's disease shows altered interaction with Fe65. Co-immunoprecipitation, mutagenesis The Journal of biological chemistry High 9045663
1998 The N-terminal PID1 domain of Fe65 binds the transcription factor CP2/LSF/LBP1 in vivo (co-immunoprecipitation), and Fe65 is present in both nuclear and non-nuclear fractions; a small region N-terminal to the WW domain is phosphorylated and required for nuclear localization. Yeast interaction trap, co-immunoprecipitation, subcellular fractionation, deletion mutagenesis The Journal of biological chemistry High 9685356
1999 FE65 co-localizes with APP in the ER/Golgi and possibly endosomes, increases translocation of APP to the cell surface, and increases both sAPPα and Aβ secretion approximately 4-fold. Co-localization (immunofluorescence), cell surface biotinylation, ELISA for secreted APP and Aβ The Journal of biological chemistry High 10075692
2000 APP functions as a cytosolic anchor that prevents Fe65 nuclear translocation: overexpression of APP blocks GFP-Fe65 nuclear entry, while Fe65 mutants unable to bind APP still translocate to the nucleus in the presence of APP. The WW domain of Fe65 is required for its nuclear translocation. GFP fusion protein imaging in transfected COS7 cells, deletion mutagenesis, nuclear fractionation of PC12 cells The Journal of biological chemistry High 11085987
2001 The cytoplasmic tail of APP forms a multimeric complex with Fe65 and the histone acetyltransferase Tip60, and this complex potently stimulates transcription via heterologous Gal4/LexA DNA binding domains, suggesting gamma-secretase cleavage of APP releases a transcriptionally active AICD-Fe65-Tip60 complex. Co-immunoprecipitation, transcription reporter assays (Gal4/LexA fusion system) Science High 11441186
2001 The APP intracellular domain (AICD/C60) is stabilized by forming complexes with Fe65 and can then enter the nucleus in neurons and non-neural cells; without Fe65, AICD is highly labile. Transfection of AICD expression plasmid, co-immunoprecipitation, subcellular localization by microscopy The Journal of biological chemistry High 11544248
2001 APP and FE65 co-localize with actin and Mena in lamellipodia and concentrate with β1-integrin in focal complexes; overexpression of APP accelerates cell migration, and co-expression with FE65 dramatically enhances this effect by increasing APP at the cell surface. Immunofluorescence co-localization, wound-healing cell migration assay, cell surface quantification The Journal of cell biology High 11425871
2001 FE65 constitutes a functional link in a trimeric LRP-FE65-APP complex: the N-terminal PTB domain of FE65 interacts with the LRP intracellular domain, the C-terminal PTB domain with APP, and FE65 knockdown by RNAi mimics the LRP knockout phenotype on APP processing. FE65 is required for LRP-mediated effects on APP secretion. Co-immunoprecipitation, GST pulldown, RNAi knockdown, APP secretion assay The Journal of neuroscience High 15115822
2001 The amino Fe65 PTB domain has close proximity to the LRP cytoplasmic domain and the carboxyl Fe65 PTB domain has close proximity to the APP cytoplasmic domain, as shown by FRET, confirming that Fe65 bridges LRP and APP intracellularly. FRET (fluorescence resonance energy transfer) in H4 cells The Journal of neuroscience Medium 11606623
2001 Phosphorylation of APP at Thr-668 diminishes its interaction with Fe65 by causing a conformational change in the cytoplasmic domain, and Fe65 binding suppresses APP maturation and Aβ production in a Thr-668-dependent manner. Site-directed mutagenesis, co-immunoprecipitation, Aβ ELISA The Journal of biological chemistry High 11517218
2002 The gamma-secretase-generated APP C-terminal domain (GFP-tagged) translocates to the nucleus in a manner dependent upon stabilization by Fe65; an APP mutation blocking Fe65 interaction prevents nuclear detection. APP-CT and Fe65 continue to interact in the nucleus as shown by FRET. Confocal microscopy with GFP fusion, FRET, site-directed mutagenesis Journal of neurochemistry High 12358789
2002 Fe65 overexpression blocks G1→S cell cycle progression by completely abolishing LSF/CP2/LBP1-driven activation of the thymidylate synthase (TS) gene; this effect requires nuclear localization of Fe65 and is abolished by co-expression of APP. The inhibitory effect is rescued by thymidine addition in fibroblasts but not in PC12 neuronal cells. Cell cycle analysis, reporter gene assay, Western blotting for TS, thymidine rescue experiment The Journal of biological chemistry High 12089154
2002 C. elegans feh-1 (Fe65 orthologue) is required for pharyngeal pumping and viability; feh-1 and apl-1 (APP orthologue) function in the same pathway controlling pharyngeal contraction, as their loss-of-function phenotypes are similar and feh-1 PTB2 domain binds apl-1. Deletion mutant generation, RNAi, genetic epistasis, binding assay, immunostaining Journal of cell science High 11896189
2003 FE65 family members stabilize APLP1 and APLP2 intracellular domains (ICDs) generated by presenilin-dependent gamma-secretase cleavage and facilitate their nuclear translocation, analogous to APP-AICD. Biochemical fractionation, co-transfection, immunoblotting Biochemistry Medium 12779321
2003 FE65 and APP co-localize with Mena in actin-rich lamellipodia of neuronal growth cones in vitro and in vivo; APP and FE65 interact in nerve terminals and associate with Rab5-containing synaptic organelles but not synaptic vesicles. Immunofluorescence, live imaging, subcellular fractionation, co-localization The Journal of neuroscience High 12843239
2003 AICD in combination with Fe65 activates gene transcription through a Tip60-dependent mechanism requiring a complex of AID-Fe65-Tip60, whereas JIP-1-induced activation is Tip60-independent, distinguishing two mechanistically distinct transcriptional pathways. Transcription reporter assay, co-immunoprecipitation, Tip60 inhibition Proceedings of the National Academy of Sciences Medium 12563035
2003 The LRP intracellular domain (LRPICD) is translocated to the nucleus and colocalizes with Tip60; LRPICD dramatically inhibits APP-AICD/Fe65 transactivation mediated by Tip60 and shows close proximity to Tip60 by FRET. FRET, transcription reporter assay, subcellular localization The Journal of biological chemistry Medium 12888553
2004 The c-Abl tyrosine kinase phosphorylates Fe65 on tyrosine 547 within its second PTB domain, and this phosphorylation stimulates APP/Fe65-mediated gene transcription. In vitro kinase assay, site-directed mutagenesis (Y547), transcription reporter assay The Journal of biological chemistry High 15031292
2004 C. elegans feh-1 mutants have decreased acetylcholinesterase activity and reduced ace-1 and ace-2 transcript levels, linking the Fe65-APP complex to regulation of acetylcholinesterase gene expression. Genetic mutant analysis, enzymatic activity assay, RT-PCR The European journal of neuroscience Medium 15355315
2004 AlcICD (Alcadein intracellular domain) suppresses FE65-dependent gene transactivation by competing with AICD for FE65 binding, demonstrating that coordinated metabolism of Alcs and APP reciprocally regulates FE65-dependent transcription. Transcription reporter assay, co-immunoprecipitation, competition binding The Journal of biological chemistry Medium 15037614
2005 Fe65 transcription activation domain overlaps with its WW domain and binds the nucleosome assembly factor SET; SET is required for Fe65-mediated transactivation of a reporter gene. Two-step ChIP demonstrates Fe65/AICD/Tip60/SET complex associates with the KAI1 gene promoter, and SET is required for basal KAI1 transcription. Reporter gene assay, RNAi knockdown, chromatin immunoprecipitation (ChIP), co-immunoprecipitation EMBO reports High 15592452
2005 The 97-kDa FE65 isoform (p97FE65) can be endoproteolytically cleaved to generate a 65-kDa C-terminal fragment (p65FE65) with up to 40-fold higher affinity for APP that potently suppresses sAPPα secretion by up to 90%. This cleavage activity is high in human/primate cells but low in rodent cells. Immunoblotting, pull-down assay, APP secretion ELISA, cell density manipulation The Journal of biological chemistry Medium 15647266
2005 Tau associates with Fe65 in vivo and in vitro via its N-terminal domain interacting with the PTB1 domain of Fe65; this interaction is regulated by phosphorylation of Tau at GSK3β and Cdk5 sites and requires an intact microtubule network. Tau-Fe65-APP complexes can form. Co-immunoprecipitation, co-localization, FRET, deletion mutagenesis Neurobiology of disease Medium 15686969
2005 FE65 itself is the dominant transcriptional activator in Gal4DB-mediated signaling; APP has modest stimulatory effects but is not absolutely required, while Tip60 acts as an FE65-associated repressor in this context. Gal4-FE65 fusion reporter assay, RNAi knockdown of APP and Tip60, overexpression The Journal of biological chemistry Medium 16332686
2006 FE65 binds to ApoEr2 via its N-terminal PTB domain; full-length FE65 increases surface expression of ApoEr2 and co-immunoprecipitation of ApoEr2 with APP. Constructs with both PTB domains (but not single PTB domain constructs) increased secreted APP, APP-CTF, secreted ApoEr2, and ApoEr2-CTF, and decreased Aβ. Co-immunoprecipitation, surface biotinylation, ELISA, domain deletion constructs The Journal of biological chemistry Medium 16638748
2006 Fe65 plays an essential role in the cellular response to DNA damage: Fe65 knockout fibroblasts show increased sensitivity to genotoxic agents (etoposide, H2O2) and ionizing radiation (elevated γ-H2AX and p53). Nuclear Fe65 undergoes rapid phosphorylation after DNA damage, and genotoxic stress induces γ-secretase cleavage of APP C-terminal fragments in a Fe65-dependent manner. Fe65 KO mice, MEF survival assay, γ-H2AX/p53 immunoblotting, APP processing analysis The Journal of biological chemistry High 17121854
2006 Phosphorylation of APP at Thr-668 liberates membrane-bound FE65 which then translocates to the nucleus to up-regulate AICD-mediated gene transactivation; non-phosphorylated AICD is dominantly found in the nucleus independently of FE65, indicating FE65 does not accompany AICD into the nucleus. Subcellular fractionation, phospho-mutant analysis, reporter gene assay Genes to cells Medium 16716194
2006 Fe65 knockout mice and FE65/FE65L1 double knockout mice develop cortical dysplasia including heterotopias and aberrant cortical projections; FE65 proteins are required for basement membrane assembly, and this phenotype resembles triple APP/APLP1/APLP2 knockout mice, placing Fe65 downstream of APP family signaling in cortical development. Targeted gene deletion (KO mice), histology, laminin organization assay with meningeal fibroblasts, genetic epistasis The EMBO journal High 16407979
2006 RNAi silencing of Fe65 increases APP-CTF levels while decreasing Aβ levels, suggesting Fe65 modulates the balance between APP C-terminal fragment accumulation and Aβ production. RNAi, Western blotting, ELISA The Journal of biological chemistry Medium 17170108
2007 The crystal structure of the human FE65 WW domain bound to polyproline peptides from Mena was determined; both peptides adopt a PPII helix and bind in a forward orientation via an induced-fit mechanism that forms the XP2 groove through movements of W271 and Y269 side-chains upon ligand binding. X-ray crystallography, structural analysis Journal of molecular biology High 17686488
2007 Fe65 stimulates γ-secretase-mediated liberation of AICD through enhanced production of APP-CTF substrates and direct stimulation of γ-secretase processing; this stimulation is isoform-dependent and inversely correlated with Aβ42 production. APP processing assays, ELISA, isoform-specific expression The Journal of biological chemistry Medium 17855370
2007 A macromolecular complex of APP and FE65 (likely including a WW-domain ligand) is a negative regulator of axon branching in hippocampal neurons; FE65 mutants unable to interact with APP (PID2 mutants) or WW mutants both increase axon branching and decrease axon segment length. Adenoviral transduction of interaction-deficient FE65 mutants in cultured hippocampal neurons, morphometric analysis Molecular and cellular neurosciences Medium 17383198
2007 Notch1 intracellular domain (Notch1-IC) physically interacts with AICD, Fe65, and Tip60, disrupting the AICD-Fe65-Tip60 trimeric complex and suppressing AICD-mediated ROS generation and cell death. Co-immunoprecipitation, reporter assay, ROS measurement, cell death assay Biochimica et biophysica acta Medium 17368826
2008 TAG1, an extracellular ligand of APP, triggers Fe65-dependent transcriptional activity by increasing AICD release in a γ-secretase-dependent manner. Genetic epistasis shows TAG1-induced correction of neurogenesis phenotype requires Fe65: it is abolished in Fe65-/- mice and by AICD mutated at the Fe65-binding site. Co-immunoprecipitation, reporter assay, genetic knockouts (TAG1-/-, APP-/-, Fe65-/-), BrdU birth tracing Nature cell biology High 18278038
2008 The crystal structure of AICD in complex with Fe65-PTB2 was determined; the interface involves the NPxY motif and two α-helices of AICD. The N-terminal helix is capped by Thr668, and mutagenesis + ITC + NMR confirm that Thr668 phosphorylation disrupts complex formation through a molecular switch mechanism. X-ray crystallography, isothermal titration calorimetry, NMR, site-directed mutagenesis EMBO reports High 18833287
2008 Dexras1 (a Ras family small GTPase) binds to the FE65 PTB2 domain and potently suppresses FE65-APP-mediated transcription; this suppression is not via competition for APP binding (both Dexras1 and APP can simultaneously bind PTB2). Phosphorylation of Fe65 Tyr547 reduces Dexras1-FE65 binding and thereby enhances transcription. Co-immunoprecipitation, reporter gene assay, siRNA knockdown, mutagenesis The Journal of biological chemistry Medium 18922798
2008 Stress (sorbitol treatment) induces APP phosphorylation via a stress-activated kinase, liberating membrane-tethered FE65 which then translocates to the nuclear matrix forming patched structures. Nuclear FE65 induces γH2AX. The APP intracellular domain fragment suppresses this nuclear targeting of liberated FE65. Subcellular fractionation, immunofluorescence, γH2AX detection, kinase inhibitor experiments The Journal of biological chemistry Medium 18468999
2009 Fe65 is required for Tip60-TRRAP complex recruitment to DNA double-strand breaks and for histone H4 acetylation at break sites; Fe65 knockdown reduces H4 acetylation and DNA repair efficiency. A Fe65 mutant unable to bind APP fails to rescue these phenotypes, and APP/APLP2 suppression similarly impairs Tip60-TRRAP recruitment. ChIP, Fe65 knockdown, H4 acetylation assay, DNA repair efficiency (comet assay/γH2AX), mutagenesis Proceedings of the National Academy of Sciences High 19282473
2009 Phosphorylation of APP Tyr-682 inhibits its interaction with Fe65, Fe65L1, and Fe65L2, as well as the interaction of all three Fe65 family members with APLP1 and APLP2, providing a second mechanism (besides secretase processing) for regulating Fe65 nuclear signaling. Co-immunoprecipitation with phospho-mimetic/phospho-null mutants, binding assays Journal of Alzheimer's disease Medium 19221419
2005 Fe65 binds the P2X2 purinergic receptor subunit C-terminal domain (but not the P2X2b splice variant lacking this region); Fe65 co-localizes with P2X2 at postsynaptic specializations of CA1 hippocampal excitatory synapses by electron microscopy immunogold labeling. Assembly with Fe65 inhibits the time- and activation-dependent change in ionic selectivity (permeability dilation) of P2X2 receptors. Yeast two-hybrid, GST pulldown, co-immunoprecipitation from brain extracts, postembedding immunogold EM, electrophysiology The Journal of biological chemistry High 16330549
2005 14-3-3γ binds both AICD and FE65 simultaneously, facilitating FE65-dependent gene transactivation by enhancing AICD-FE65 association. 14-3-3γ binds AICD at the 667VTPEER672 motif; Thr-668 phosphorylation inhibits this interaction. 14-3-3γ binds FE65 via a sequence between the WW domain and PTB1. Co-immunoprecipitation, reporter gene assay, mutagenesis, deletion analysis The Journal of biological chemistry Medium 16223726
2009 FE65 binds Teashirt proteins (identified by yeast two-hybrid with Fe65 PTB domain); FE65 simultaneously recruits SET and Teashirt (which recruits histone deacetylases) to form a gene-silencing complex. ChIP shows direct interaction of FE65 and Teashirt3 with the CASP4 promoter, and this complex silences caspase-4 expression. Yeast two-hybrid, reporter assay, ChIP, co-immunoprecipitation PloS one Medium 19343227
2011 Phosphorylation of LRP1 NPVY(4507) motif regulates its interaction with Fe65-PTB1 in an insulin receptor substrate-like manner; Fe65-PTB1 directly interacts with the distal NPVY motif of the LRP1 intracellular domain in a phosphorylation-dependent manner. Biochemical binding assays, biophysical methods (NMR/ITC implied), phospho-peptide analysis FEBS letters Medium 21968187
2012 Fe65 interacts with huntingtin (Htt) via WW-polyproline interaction in a polyglutamine length-dependent manner; Fe65 knockdown reduces mutant Htt protein levels via the ubiquitin-proteasome system (UPS) and increases mutant Htt ubiquitination, suggesting Fe65 protects mutant Htt from UPS-mediated degradation. Co-immunoprecipitation, knockdown, ubiquitination assay, proteasome inhibitor experiments The Biochemical journal Medium 22352297
2012 The AICD/FE65/TIP60 ternary complex down-regulates Stathmin1 expression; proteomics of AFT-expressing cells vs. controls identified Stathmin1 as significantly reduced, validated by label-free MS and a reversal model with APP family knockdown. Stable isotope labeling proteomics, label-free MS, knockdown validation Biochimica et biophysica acta Medium 22902274
2013 Fe65 via its PTB1 domain binds ARF6 (preferentially ARF6-GDP) and stimulates activation of ARF6 and downstream Rac1; Fe65 and ARF6 co-localize in neuronal growth cones and together promote neurite outgrowth via Rac1 signaling. ARF6 knockdown attenuates FE65-stimulated neurite outgrowth. Co-immunoprecipitation, GTPase activation assay, siRNA knockdown, neurite outgrowth assay FASEB journal High 24056087
2013 Fe65 is the bridging protein in a novel trimeric AβPP:Fe65:PP1γ complex; Fe65 interacts with PP1γ (demonstrated by yeast tri-hybrid, overlay assay, and co-immunoprecipitation), and this complex correlates with AβPP Thr668 phosphorylation state. Yeast tri-hybrid, co-immunoprecipitation, overlay assay Journal of Alzheimer's disease Medium 23531501
2013 FE65 interacts with SV2A and SERCA2 in human brain (validated by co-immunoprecipitation); FE65/FE65L1 double KO neurons show elevated SERCA2 levels, and FE65 knockdown in HEK293T cells elevates sensitivity to thapsigargin (SERCA inhibitor), implicating FE65 in regulation of intracellular calcium homeostasis via SERCA2. Pulldown/mass spectrometry from human brain, co-immunoprecipitation, KO neuron proteomics, thapsigargin sensitivity assay Molecular & cellular proteomics Medium 24284412
2013 FE65 regulates and interacts with the Bloom syndrome protein (BLM) in dynamic nuclear spheres; FE65 knockdown causes downregulation of BLM and MCM proteins, while elevated nuclear FE65 stabilizes BLM in nuclear mobile spheres that can grow and fuse. FE65 knockdown reduces cell replication. RNAi knockdown, immunofluorescence, live cell imaging, proliferation assay Journal of cell science Medium 23572515
2015 SGK1 phosphorylates FE65 on Ser610, attenuating FE65 binding to APP; FE65 Ser610 phosphorylation inhibits FE65-promoted amyloidogenic APP processing and FE65-mediated APP degradation via the proteasome. In vitro kinase assay, site-directed mutagenesis, co-immunoprecipitation, APP processing assay, proteasome inhibitor experiments The Biochemical journal High 26188042
2015 Fe65 suppresses breast cancer cell migration and invasion through its PTB1 domain recruiting Tip60 to cortactin to stimulate cortactin acetylation. Cell migration/invasion assay, co-immunoprecipitation, acetylation assay, domain deletion constructs Scientific reports Medium 26166158
2018 FE65 interacts with ELMO1 via its N-terminal region, activates ELMO1 by diminishing its intramolecular autoinhibitory interaction, promotes ELMO1 targeting to the plasma membrane, and forms a tripartite FE65-ELMO1-DOCK180 complex that activates Rac1 to stimulate neurite outgrowth. Co-immunoprecipitation, ELMO1 autoinhibition assay, membrane fractionation, Rac1 activation assay, neurite outgrowth assay, siRNA knockdown The Journal of biological chemistry High 29615491
2020 FE65 potentiates ARF6-Rac1 signaling by serving as a functional link between ARF6 and ELMO1, promoting plasma membrane trafficking of ELMO1 via the endosomal recycling pathway; FE65 KO reduces ELMO1 in recycling endosomes and at the plasma membrane. Co-immunoprecipitation, Rac1 activation assay, recycling endosome fractionation, neurite outgrowth assay, FE65 KO cells FASEB journal High 33047393
2003 Fe65 is phosphorylated on specific in vivo residues by ERK1/2 MAP kinases, as identified by mass spectrometry sequencing of Fe65 from cells. In vitro kinase assay, mass spectrometry phosphosite identification Molecular and cellular neurosciences Medium 14697653

Source papers

Stage 0 corpus · 100 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2001 A transcriptionally [correction of transcriptively] active complex of APP with Fe65 and histone acetyltransferase Tip60. Science (New York, N.Y.) 1016 11441186
1996 The phosphotyrosine interaction domains of X11 and FE65 bind to distinct sites on the YENPTY motif of amyloid precursor protein. Molecular and cellular biology 435 8887653
2001 The intracellular domain of the beta-amyloid precursor protein is stabilized by Fe65 and translocates to the nucleus in a notch-like manner. The Journal of biological chemistry 373 11544248
1995 The regions of the Fe65 protein homologous to the phosphotyrosine interaction/phosphotyrosine binding domain of Shc bind the intracellular domain of the Alzheimer's amyloid precursor protein. The Journal of biological chemistry 267 8537337
2001 Phosphorylation-dependent regulation of the interaction of amyloid precursor protein with Fe65 affects the production of beta-amyloid. The Journal of biological chemistry 231 11517218
1997 The WW domain of neural protein FE65 interacts with proline-rich motifs in Mena, the mammalian homolog of Drosophila enabled. The Journal of biological chemistry 208 9407065
2004 FE65 constitutes the functional link between the low-density lipoprotein receptor-related protein and the amyloid precursor protein. The Journal of neuroscience : the official journal of the Society for Neuroscience 192 15115822
2001 The Alzheimer amyloid precursor protein (APP) and FE65, an APP-binding protein, regulate cell movement. The Journal of cell biology 191 11425871
1999 Regulation of beta-amyloid secretion by FE65, an amyloid protein precursor-binding protein. The Journal of biological chemistry 190 10075692
2008 A TAG1-APP signalling pathway through Fe65 negatively modulates neurogenesis. Nature cell biology 181 18278038
1996 Association of a novel human FE65-like protein with the cytoplasmic domain of the beta-amyloid precursor protein. Proceedings of the National Academy of Sciences of the United States of America 154 8855266
2003 The amyloid precursor protein and its regulatory protein, FE65, in growth cones and synapses in vitro and in vivo. The Journal of neuroscience : the official journal of the Society for Neuroscience 146 12843239
1997 Interaction of the phosphotyrosine interaction/phosphotyrosine binding-related domains of Fe65 with wild-type and mutant Alzheimer's beta-amyloid precursor proteins. The Journal of biological chemistry 139 9045663
1998 The Fe65 adaptor protein interacts through its PID1 domain with the transcription factor CP2/LSF/LBP1. The Journal of biological chemistry 135 9685356
2001 Demonstration by fluorescence resonance energy transfer of two sites of interaction between the low-density lipoprotein receptor-related protein and the amyloid precursor protein: role of the intracellular adapter protein Fe65. The Journal of neuroscience : the official journal of the Society for Neuroscience 124 11606623
2006 Essential roles for the FE65 amyloid precursor protein-interacting proteins in brain development. The EMBO journal 119 16407979
2000 The beta-amyloid precursor protein functions as a cytosolic anchoring site that prevents Fe65 nuclear translocation. The Journal of biological chemistry 119 11085987
2008 The FE65 proteins and Alzheimer's disease. Journal of neuroscience research 114 17828772
1996 cDNA cloning and chromosome mapping of the human Fe65 gene: interaction of the conserved cytoplasmic domains of the human beta-amyloid precursor protein and its homologues with the mouse Fe65 protein. Human molecular genetics 108 8894693
2023 Fe65-engineered neuronal exosomes encapsulating corynoxine-B ameliorate cognition and pathology of Alzheimer's disease. Signal transduction and targeted therapy 104 37867176
1998 Fe65 and the protein network centered around the cytosolic domain of the Alzheimer's beta-amyloid precursor protein. FEBS letters 100 9738440
2003 The intracellular domain of the low density lipoprotein receptor-related protein modulates transactivation mediated by amyloid precursor protein and Fe65. The Journal of biological chemistry 95 12888553
2003 gamma-Secretase cleavage and binding to FE65 regulate the nuclear translocation of the intracellular C-terminal domain (ICD) of the APP family of proteins. Biochemistry 90 12779321
1998 Fe65L2: a new member of the Fe65 protein family interacting with the intracellular domain of the Alzheimer's beta-amyloid precursor protein. The Biochemical journal 86 9461550
2005 Transcription regulation by the adaptor protein Fe65 and the nucleosome assembly factor SET. EMBO reports 82 15592452
2002 Direct visualization of the gamma secretase-generated carboxyl-terminal domain of the amyloid precursor protein: association with Fe65 and translocation to the nucleus. Journal of neurochemistry 82 12358789
2004 Coordinated metabolism of Alcadein and amyloid beta-protein precursor regulates FE65-dependent gene transactivation. The Journal of biological chemistry 77 15037614
2006 Role of APP phosphorylation in FE65-dependent gene transactivation mediated by AICD. Genes to cells : devoted to molecular & cellular mechanisms 72 16716194
2002 Fe65, a ligand of the Alzheimer's beta-amyloid precursor protein, blocks cell cycle progression by down-regulating thymidylate synthase expression. The Journal of biological chemistry 72 12089154
2008 Structure of the intracellular domain of the amyloid precursor protein in complex with Fe65-PTB2. EMBO reports 70 18833287
2004 The c-Abl tyrosine kinase phosphorylates the Fe65 adaptor protein to stimulate Fe65/amyloid precursor protein nuclear signaling. The Journal of biological chemistry 65 15031292
2006 FE65 interaction with the ApoE receptor ApoEr2. The Journal of biological chemistry 64 16638748
2003 JNK-interacting protein-1 promotes transcription of A beta protein precursor but not A beta precursor-like proteins, mechanistically different than Fe65. Proceedings of the National Academy of Sciences of the United States of America 64 12563035
1997 DNA-binding protein Pur alpha and transcription factor YY1 function as transcription activators of the neuron-specific FE65 gene promoter. The Biochemical journal 62 9359867
2004 Isoform-specific knockout of FE65 leads to impaired learning and memory. Journal of neuroscience research 61 14689444
2005 Role of 14-3-3gamma in FE65-dependent gene transactivation mediated by the amyloid beta-protein precursor cytoplasmic fragment. The Journal of biological chemistry 57 16223726
2007 Epigallocatechin gallate (EGCG) suppresses beta-amyloid-induced neurotoxicity through inhibiting c-Abl/FE65 nuclear translocation and GSK3 beta activation. Neurobiology of aging 55 17590240
1998 The human FE65 gene: genomic structure and an intronic biallelic polymorphism associated with sporadic dementia of the Alzheimer type. Human genetics 55 9799084
2010 Megalin interacts with APP and the intracellular adapter protein FE65 in neurons. Molecular and cellular neurosciences 54 20637285
2009 Fe65 is required for Tip60-directed histone H4 acetylation at DNA strand breaks. Proceedings of the National Academy of Sciences of the United States of America 50 19282473
2005 A dominant role for FE65 (APBB1) in nuclear signaling. The Journal of biological chemistry 49 16332686
2002 Expression of the Fe65 adapter protein in adult and developing mouse brain. Neuroscience 48 12435432
2017 Identification of Small Molecule Translesion Synthesis Inhibitors That Target the Rev1-CT/RIR Protein-Protein Interaction. ACS chemical biology 47 28541665
2006 Essential roles for Fe65, Alzheimer amyloid precursor-binding protein, in the cellular response to DNA damage. The Journal of biological chemistry 47 17121854
2006 RNA interference silencing of the adaptor molecules ShcC and Fe65 differentially affect amyloid precursor protein processing and Abeta generation. The Journal of biological chemistry 47 17170108
2005 Expression of human FE65 in amyloid precursor protein transgenic mice is associated with a reduction in beta-amyloid load. Journal of neurochemistry 45 15816856
2002 feh-1 and apl-1, the Caenorhabditis elegans orthologues of mammalian Fe65 and beta-amyloid precursor protein genes, are involved in the same pathway that controls nematode pharyngeal pumping. Journal of cell science 45 11896189
2008 Dexras1 interacts with FE65 to regulate FE65-amyloid precursor protein-dependent transcription. The Journal of biological chemistry 43 18922798
2000 Fe65 and X11beta co-localize with and compete for binding to the amyloid precursor protein. Neuroreport 42 11095528
2007 Structural basis for polyproline recognition by the FE65 WW domain. Journal of molecular biology 41 17686488
2008 Regulation of FE65 nuclear translocation and function by amyloid beta-protein precursor in osmotically stressed cells. The Journal of biological chemistry 39 18468999
2009 FE65 binds Teashirt, inhibiting expression of the primate-specific caspase-4. PloS one 37 19343227
2012 A ternary complex consisting of AICD, FE65, and TIP60 down-regulates Stathmin1. Biochimica et biophysica acta 36 22902274
2005 Fe65 interacts with P2X2 subunits at excitatory synapses and modulates receptor function. The Journal of biological chemistry 36 16330549
2013 FE65 interacts with ADP-ribosylation factor 6 to promote neurite outgrowth. FASEB journal : official publication of the Federation of American Societies for Experimental Biology 33 24056087
2012 FE65 as a link between VLDLR and APP to regulate their trafficking and processing. Molecular neurodegeneration 32 22429478
2011 A role for FE65 in controlling GnRH-1 neurogenesis. The Journal of neuroscience : the official journal of the Society for Neuroscience 32 21228158
1994 Expression of the neuron-specific FE65 gene marks the development of embryo ganglionic derivatives. Developmental neuroscience 32 7867517
2013 Amyloid beta a4 precursor protein-binding family B member 1 (FE65) interactomics revealed synaptic vesicle glycoprotein 2A (SV2A) and sarcoplasmic/endoplasmic reticulum calcium ATPase 2 (SERCA2) as new binding proteins in the human brain. Molecular & cellular proteomics : MCP 31 24284412
2007 A macromolecular complex involving the amyloid precursor protein (APP) and the cytosolic adapter FE65 is a negative regulator of axon branching. Molecular and cellular neurosciences 31 17383198
2009 Phosphorylation of a tyrosine in the amyloid-beta protein precursor intracellular domain inhibits Fe65 binding and signaling. Journal of Alzheimer's disease : JAD 30 19221419
2005 Interaction of Tau with Fe65 links tau to APP. Neurobiology of disease 30 15686969
2003 The transcriptional activity of the APP intracellular domain-Fe65 complex is inhibited by activation of the NF-kappaB pathway. Biochemistry 30 12653567
2000 A FE65 polymorphism associated with risk of developing sporadic late-onset alzheimer's disease but not with Abeta loading in brains. Neuroscience letters 30 11065130
2001 FE65 in Alzheimer's disease: neuronal distribution and association with neurofibrillary tangles. The American journal of pathology 28 11337355
2013 Identification of a novel complex AβPP:Fe65:PP1 that regulates AβPP Thr668 phosphorylation levels. Journal of Alzheimer's disease : JAD 27 23531501
2007 Fe65 stimulates proteolytic liberation of the beta-amyloid precursor protein intracellular domain. The Journal of biological chemistry 27 17855370
2006 Suppression of beta-amyloid precursor protein signaling into the nucleus by estrogens mediated through complex formation between the estrogen receptor and Fe65. Molecular and cellular biology 27 17130235
2012 Degradation of mutant huntingtin via the ubiquitin/proteasome system is modulated by FE65. The Biochemical journal 26 22352297
2009 The APP-interacting protein FE65 is required for hippocampus-dependent learning and long-term potentiation. Learning & memory (Cold Spring Harbor, N.Y.) 26 19713352
2000 Broadly altered expression of the mRNA isoforms of FE65, a facilitator of beta amyloidogenesis, in Alzheimer cerebellum and other brain regions. Journal of neuroscience research 26 10723070
2006 Taking down the unindicted co-conspirators of amyloid beta-peptide-mediated neuronal death: shared gene regulation of BACE1 and APP genes interacting with CREB, Fe65 and YY1 transcription factors. Current Alzheimer research 25 17168646
2018 Neuronal adaptor FE65 stimulates Rac1-mediated neurite outgrowth by recruiting and activating ELMO1. The Journal of biological chemistry 24 29615491
2015 Fe65 Suppresses Breast Cancer Cell Migration and Invasion through Tip60 Mediated Cortactin Acetylation. Scientific reports 24 26166158
2015 Phosphorylation of FE65 Ser610 by serum- and glucocorticoid-induced kinase 1 modulates Alzheimer's disease amyloid precursor protein processing. The Biochemical journal 24 26188042
2007 Notch1 intracellular domain suppresses APP intracellular domain-Tip60-Fe65 complex mediated signaling through physical interaction. Biochimica et biophysica acta 24 17368826
2005 Endoproteolytic cleavage of FE65 converts the adaptor protein to a potent suppressor of the sAPPalpha pathway in primates. The Journal of biological chemistry 24 15647266
2004 Fe65 is not involved in the platelet-derived growth factor-induced processing of Alzheimer's amyloid precursor protein, which activates its caspase-directed cleavage. The Journal of biological chemistry 24 14766758
2002 A candidate molecular mechanism for the association of an intronic polymorphism of FE65 with resistance to very late onset dementia of the Alzheimer type. Human molecular genetics 24 11854179
2003 Real-time PCR quantitation of FE65 a beta-amyloid precursor protein-binding protein after traumatic brain injury in rats. International journal of legal medicine 23 12707777
1999 Alternatively spliced isoforms of FE65 serve as neuron-specific and non-neuronal markers. Journal of neuroscience research 23 10561691
2003 The neuronal adaptor protein Fe65 is phosphorylated by mitogen-activated protein kinase (ERK1/2). Molecular and cellular neurosciences 22 14697653
2002 Low-density lipoprotein receptor-related protein levels and endocytic function are reduced by overexpression of the FE65 adaptor protein, FE65L1. Journal of neurochemistry 21 12358780
2016 FE65 and FE65L1 share common synaptic functions and genetically interact with the APP family in neuromuscular junction formation. Scientific reports 20 27734846
2013 FE65 regulates and interacts with the Bloom syndrome protein in dynamic nuclear spheres - potential relevance to Alzheimer's disease. Journal of cell science 19 23572515
2012 The amyloid precursor protein intracellular domain-fe65 multiprotein complexes: a challenge to the amyloid hypothesis for Alzheimer's disease? International journal of Alzheimer's disease 19 22506131
2012 Fe65 matters: new light on an old molecule. IUBMB life 18 23129269
2009 Alphabeta hinders nuclear targeting of AICD and Fe65 in primary neuronal cultures. Journal of molecular neuroscience : MN 18 19340611
2019 Effects of the Pentapeptide P33 on Memory and Synaptic Plasticity in APP/PS1 Transgenic Mice: A Novel Mechanism Presenting the Protein Fe65 as a Target. International journal of molecular sciences 17 31234498
2015 FE65: Roles beyond amyloid precursor protein processing. Cellular & molecular biology letters 17 26204394
2011 Phosphorylation of LRP1 regulates the interaction with Fe65. FEBS letters 17 21968187
2004 Mutation of the feh-1 gene, the Caenorhabditis elegans orthologue of mammalian Fe65, decreases the expression of two acetylcholinesterase genes. The European journal of neuroscience 17 15355315
2000 Evidence against association of the FE65 gene (APBB1) intron 13 polymorphism in Alzheimer's patients. Neuroscience letters 17 11099823
2020 ARF6-Rac1 signaling-mediated neurite outgrowth is potentiated by the neuronal adaptor FE65 through orchestrating ARF6 and ELMO1. FASEB journal : official publication of the Federation of American Societies for Experimental Biology 16 33047393
2017 The Rev1 interacting region (RIR) motif in the scaffold protein XRCC1 mediates a low-affinity interaction with polynucleotide kinase/phosphatase (PNKP) during DNA single-strand break repair. The Journal of biological chemistry 16 28821613
2016 APBB1 reinforces cancer stem cell and epithelial-to-mesenchymal transition by regulating the IGF1R signaling pathway in non-small-cell lung cancer cells. Biochemical and biophysical research communications 16 27836546
2011 Chromatin acetylation, β-amyloid precursor protein and its binding partner FE65 in DNA double strand break repair. Acta biochimica Polonica 16 21403922
2008 C-terminal 37 residues of LRP promote the amyloidogenic processing of APP independent of FE65. Journal of cellular and molecular medicine 16 18373737
2011 FE65 proteins regulate NMDA receptor activation-induced amyloid precursor protein processing. Journal of neurochemistry 15 21824144
2000 No association between an intronic biallelic polymorphism of the FE65 gene and Alzheimer's disease. International journal of molecular medicine 15 11029529

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