Affinage

RB1CC1

RB1-inducible coiled-coil protein 1 · UniProt Q8TDY2

Length
1594 aa
Mass
183.1 kDa
Annotated
2026-06-10
100 papers in source corpus 33 papers cited in narrative 32 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

RB1CC1/FIP200 is a large dimeric scaffold protein that serves as the organizing node of autophagy initiation while also functioning in autophagy-independent signaling and transcription (PMID:18443221, PMID:19211835). As a core subunit of the ULK1–ATG13–FIP200–ATG101 complex, it is required for autophagosome formation: it localizes to the isolation membrane, supports ULK1 stability and kinase activity, and—together with ATG13—maximally stimulates ULK1 in reconstituted reactions (PMID:18443221, PMID:19258318). Within this complex, FIP200 is a dimer whose N-terminal domain adopts a C-shaped conformation that binds the C-terminal IDR of ATG13 via a critical LQFL motif (residues 582–585), while its coiled-coil region mediates membrane and NDP52 binding (PMID:27013233, PMID:32516362, PMID:32773036); mTORC1 is incorporated through ULK1 and phosphorylates ULK1 and ATG13 to suppress autophagy under nutrient-replete conditions (PMID:19211835). FIP200 bridges the ULK1 and ATG5/ATG16L1 machineries through a direct interaction with a short FIP200-binding domain in ATG16L1, governing both early and late stages of autophagosome biogenesis (PMID:23262492, PMID:23392225). Selective autophagy is coordinated through the dimeric C-terminal Claw domain, which binds phosphorylation-enhanced motifs in cargo receptors p62/SQSTM1, CCPG1, and Optineurin, coupling cargo condensation and phase separation to autophagosome biogenesis (PMID:30853400, PMID:33692357); FIP200 likewise engages NDP52/CALCOCO2 and TAX1BP1 to drive mitophagy and ubiquitin-independent cargo clearance and to set the TBK1 activation threshold at p62 condensates (PMID:33226137, PMID:32892694, PMID:34226595, PMID:38437556). Autophagy site specification is initiated when ER-surface Ca2+ transients trigger liquid–liquid phase separation of FIP200 into puncta that nucleate autophagosome formation sites, an activity dependent on its N-terminal IDR and stabilized by CREBBP-mediated acetylation at K276 that protects FIP200 from ubiquitin-dependent degradation (PMID:36394358, PMID:36198318). Independently of autophagy, FIP200 acts as a kinase inhibitor binding the kinase domains of Pyk2 and FAK (PMID:10769033, PMID:12221124), translocates to the nucleus to activate transcription of RB1, p16, and p21 in complex with hSNF5 and p53 (PMID:11850849, PMID:19437535, PMID:20614030), modulates TSC1–mTOR signaling and TNFα/JNK-dependent apoptosis (PMID:16043512, PMID:17015619), and serves as a substrate-selective cofactor for Arkadia-mediated ubiquitination in TGF-β signaling (PMID:21795712). In vivo, FIP200 deletion produces autophagy-dependent neurodegeneration and apoptosis, and genetic separation-of-function knock-ins establish that its autophagic and non-autophagic activities serve distinct developmental requirements (PMID:19940130, PMID:27013233).

Mechanistic history

Synthesis pass · year-by-year structured walk · 21 steps
  1. 2000 High

    Established the first molecular function of FIP200 as a kinase inhibitor, before any autophagy role was known, by showing it binds and suppresses Pyk2.

    Evidence Yeast two-hybrid, in vitro kinase assay, and reciprocal co-IP with domain mapping

    PMID:10769033

    Open questions at the time
    • Physiological contexts where FIP200-Pyk2 dissociation is regulated not fully defined
    • Does not address structural basis of kinase-domain binding
  2. 2002 High

    Extended the kinase-inhibitor role to FAK and linked FIP200 to control of cell spreading, migration, and cell cycle, defining a cytoskeletal/adhesion signaling function.

    Evidence In vitro binding, kinase assay, domain mapping, and cell-biological assays

    PMID:12221124

    Open questions at the time
    • Whether FAK and Pyk2 inhibition occur in the same cellular pool of FIP200 unknown
    • Relationship to nuclear/transcriptional functions not addressed
  3. 2002 Medium

    Identified a nuclear, sequence-specific transcriptional activity, showing FIP200 binds the RB1 promoter and activates its transcription—a function distinct from cytoplasmic signaling.

    Evidence ChIP, EMSA, luciferase reporter, and immunocytochemistry across two papers from one group

    PMID:11850849 PMID:19437535

    Open questions at the time
    • Mechanism of regulated nuclear translocation not defined
    • Direct vs cofactor-mediated DNA binding not fully resolved
  4. 2005 Medium

    Connected FIP200 to mTOR/cell-size control and to p53 stabilization and cyclin D1 turnover, framing it as a growth and cell-cycle regulator.

    Evidence Co-IP, RNAi, half-life/pulse-chase assays, and cell size measurement

    PMID:16043512 PMID:16061648

    Open questions at the time
    • Mechanism by which FIP200 stabilizes p53 (ubiquitin/Hdm2-independent) undefined
    • Direct vs indirect effect on TSC1-TSC2 complex unresolved
  5. 2006 High

    In vivo knockout established FIP200 as required for S6K activation, cell size, and protection from TNFα-induced apoptosis via TRAF2-ASK1-JNK signaling.

    Evidence Mouse knockout with co-IP, kinase assays, and pathway dissection

    PMID:17015619

    Open questions at the time
    • Did not yet separate these phenotypes from FIP200's autophagy role
    • Direct biochemical link between FIP200 and TRAF2-ASK1 not structurally defined
  6. 2008 High

    Discovered FIP200's central role in autophagy by identifying it as a ULK1/2 interactor essential for autophagosome formation and ULK1 stability, redefining the protein's primary function.

    Evidence Co-IP, immunofluorescence localization to isolation membrane, and conditional KO MEFs

    PMID:18443221

    Open questions at the time
    • Stoichiometry and architecture of the complex not yet known
    • Mechanism of ULK1 stabilization unresolved
  7. 2009 High

    Defined the architecture and nutrient regulation of the autophagy-initiation complex, showing FIP200-ULK1-ATG13 forms a stable ~3 MDa assembly into which mTORC1 is recruited to phosphorylate ULK1 and ATG13.

    Evidence Gel filtration, mass spectrometry, co-IP, and in vitro kinase reconstitution

    PMID:19211835 PMID:19258318

    Open questions at the time
    • Precise contribution of FIP200 vs ATG13 to ULK1 activation not separated
    • Structural basis of complex assembly not yet determined
  8. 2009 High

    In vivo neural deletion demonstrated that FIP200-dependent autophagy clears ubiquitinated aggregates and damaged mitochondria, with loss causing neurodegeneration.

    Evidence Neural-specific conditional KO mouse with EM, IHC, and Western blot

    PMID:19940130

    Open questions at the time
    • Did not separate autophagy-dependent from autophagy-independent contributions to neurodegeneration
  9. 2011 Medium

    Mapped autophagy-independent functions in transcription (RB1/p16/p21 activation with hSNF5/p53) and cytoplasmic p53-mediated autophagy inhibition, expanding the protein's regulatory repertoire.

    Evidence ChIP, luciferase, co-IP, and point mutagenesis (p53 K382R)

    PMID:20614030 PMID:21775823

    Open questions at the time
    • Determinants distinguishing nuclear-transcriptional from cytoplasmic-autophagy pools of FIP200 unclear
    • Structural basis of p53-FIP200 interaction undefined
  10. 2011 Medium

    Identified FIP200 as a substrate-selective cofactor for Arkadia E3 ligase, positively regulating TGF-β signaling by promoting c-Ski ubiquitination.

    Evidence Co-IP, ubiquitination assay, and knockdown with target-gene readouts

    PMID:21795712

    Open questions at the time
    • Structural basis of substrate selectivity (c-Ski vs SnoN) unresolved
    • Single-lab finding without reconstitution
  11. 2013 High

    Showed FIP200 bridges the ULK1 and ATG5 machineries via a direct interaction with a short FIP200-binding domain in ATG16L1, controlling membrane targeting in ULK1-dependent autophagy.

    Evidence Co-IP, domain deletion mutagenesis, and autophagy flux/localization assays across two papers

    PMID:23262492 PMID:23392225

    Open questions at the time
    • Structural details of the FIP200-ATG16L1 interface not resolved
    • Whether bridging is direct contact or relayed through other factors
  12. 2016 High

    Genetically separated autophagy-dependent from -independent FIP200 functions in vivo, defining the ATG13-binding LQFL motif and showing non-autophagic functions support embryogenesis while autophagy supports neonatal survival and tumor growth.

    Evidence Point mutagenesis (FIP200-4A), conditional KO and knock-in mouse models, and autophagy flux assays

    PMID:27013233

    Open questions at the time
    • Full molecular catalog of autophagy-independent functions still incomplete
  13. 2016 High

    Defined a non-cell-autonomous consequence of FIP200 loss, where p62 aggregate-driven NF-κB activation recruits microglia that block neural stem cell differentiation.

    Evidence Conditional KO mouse with NF-κB analysis and microglia blocking/depletion rescue

    PMID:28634261

    Open questions at the time
    • Direct link from FIP200 to chemokine induction beyond p62 aggregation not detailed
  14. 2019 High

    Provided the structural mechanism for selective cargo recognition, showing the dimeric Claw domain binds disordered, phosphorylation-enhanced regions of p62 to couple cargo phase separation to degradation.

    Evidence Crystal structure, in vitro pulldown, reconstituted phase separation, and mutagenesis

    PMID:30853400

    Open questions at the time
    • Generality of Claw motif across all receptors addressed only later
    • In vivo significance of mutually exclusive p62-LC3B binding not tested
  15. 2020 High

    Resolved the overall architecture of the ULK1 complex, establishing FIP200 as a dimer whose C-shaped NTD binds ATG13 and whose coiled coil binds membranes and NDP52, with NDP52 allosterically stimulating membrane recruitment.

    Evidence Cryo-EM, HDX-MS, MALS, GUV reconstitution, and mutagenesis across multiple papers

    PMID:32516362 PMID:32773036

    Open questions at the time
    • Conformational changes upon full complex assembly on membranes not fully captured
    • How membrane binding integrates with kinase activation unresolved
  16. 2020 High

    Established FIP200 cargo-receptor axes for selective autophagy and mitophagy, showing TAX1BP1 and NDP52/CALCOCO2 recruit FIP200 to drive autophagosome formation, including LC3-lipidation-independent flux.

    Evidence Genome-wide CRISPR screens, KO cells, co-IP, and mitophagy/flux assays

    PMID:32892694 PMID:33226137

    Open questions at the time
    • Mechanism of ubiquitin-independent TAX1BP1 recruitment to NBR1 incompletely defined
    • Relative contributions of parallel axes in vivo not quantified
  17. 2020 Medium

    Identified an autophagy-independent immunoregulatory function in which FIP200 suppresses TBK1-IFN signaling by binding the adaptor AZI2, modulating anti-tumor T-cell recruitment.

    Evidence Conditional KO mouse models, co-IP, gene expression, and immune profiling

    PMID:32580962

    Open questions at the time
    • Structural basis of FIP200-AZI2 interaction undefined
    • Single-lab study
  18. 2021 High

    Generalized the phosphoregulated Claw-binding mechanism by defining a consensus motif in CCPG1 and Optineurin, and showed FIP200 sets the TBK1 activation threshold at p62 condensates via TAX1BP1.

    Evidence Crystal structures with phospho-site mutagenesis; KO cells with phosphorylation readouts

    PMID:33692357 PMID:34226595

    Open questions at the time
    • How kinases generating the phospho-marks are coordinated with FIP200 recruitment not resolved
    • TBK1-threshold finding (Medium) from a single lab
  19. 2022 High

    Defined the initiating trigger for autophagosome site specification: ER-surface Ca2+ transients drive FIP200 liquid-liquid phase separation into puncta that nucleate formation sites, with CREBBP acetylation at K276 stabilizing FIP200 and its N-terminal IDR enabling LLPS.

    Evidence Super-resolution live imaging, Ca2+ imaging, siRNA epistasis; mass spectrometry, in vitro LLPS, FRAP, and CHX chase

    PMID:36198318 PMID:36394358

    Open questions at the time
    • How Ca2+ is sensed by FIP200 to trigger phase separation mechanistically undefined
    • Interplay between acetylation, IDR, and Ca2+-triggered LLPS not fully integrated
  20. 2022 Medium

    Linked FIP200 to ferroptosis through a JNK-dependent phospho-switch (Ser537) driving nuclear translocation and ELP3-mediated histone acetylation at ferroptosis gene enhancers.

    Evidence ChIP-seq, phospho-site mutagenesis, immunofluorescence, and xenograft model

    PMID:35220675

    Open questions at the time
    • Relationship between this nuclear function and prior RB1/p21 transcriptional activity unclear
    • Single-lab finding
  21. 2024 High

    Resolved the structural basis of TAX1BP1-FIP200 engagement, defining two distinct binding sites and competition with NAP1 that can form a stabilized ternary complex.

    Evidence Crystal structure, in vitro pulldown, competition assays, and mutagenesis

    PMID:38437556

    Open questions at the time
    • Functional significance of the ternary TAX1BP1/NAP1/RB1CC1 complex in cells not established

Open questions

Synthesis pass · forward-looking unresolved questions
  • How the many autophagy-dependent and -independent functions of FIP200 are spatially and temporally partitioned within a single cell—and how its nuclear, transcriptional, kinase-inhibitory, and condensate-forming activities are switched—remains unresolved.
  • No unified model of how post-translational marks select among FIP200 functions
  • Determinants of nuclear vs cytoplasmic partitioning incompletely mapped
  • Structural basis of most autophagy-independent interactions undefined

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0060090 molecular adaptor activity 4 GO:0098772 molecular function regulator activity 3 GO:0003677 DNA binding 2 GO:0008289 lipid binding 2 GO:0140110 transcription regulator activity 2
Localization
GO:0005634 nucleus 4 GO:0005829 cytosol 3 GO:0005783 endoplasmic reticulum 1
Pathway
R-HSA-9612973 Autophagy 6 R-HSA-162582 Signal Transduction 5 R-HSA-5357801 Programmed Cell Death 2 R-HSA-74160 Gene expression (Transcription) 2
Partners
ATG13ATG16L1CALCOCO2OPTNSQSTM1TAX1BP1TSC1ULK1
Complex memberships
ULK1-ATG13-FIP200-ATG101 complex

Evidence

Reading pass · 32 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2000 FIP200 (RB1CC1) was identified as a novel inhibitor of Pyk2 kinase by yeast two-hybrid screen and confirmed by coimmunoprecipitation; FIP200 binds to the kinase domain of Pyk2 and inhibits its kinase activity in vitro kinase assays and in vivo, and dissociation of the endogenous FIP200-Pyk2 complex correlates with Pyk2 activation by biological stimuli. Yeast two-hybrid, in vitro binding, coimmunoprecipitation, in vitro kinase assay The Journal of cell biology High 10769033
2002 FIP200 (RB1CC1) associates with FAK through multiple domains and inhibits FAK kinase activity in vitro; FIP200 binds the kinase domain of FAK, inhibits FAK autophosphorylation in vivo, and overexpression inhibits cell spreading, migration, and cell cycle progression in a FAK-dependent manner. Disruption of endogenous FIP200-FAK interaction increases FAK phosphorylation. In vitro binding, coimmunoprecipitation, in vitro kinase assay, cell biological assays, domain mapping Molecular biology of the cell High 12221124
2002 RB1CC1 is localized in the nucleus and its C-terminus is required for nuclear localization. Nuclear RB1CC1 directly binds a GC-rich region 201 bp upstream of the RB1 promoter and activates RB1 transcription. Western blot, immunocytochemistry, chromatin immunoprecipitation, luciferase reporter, EMSA Oncogene / International journal of cancer Medium 11850849 19437535
2005 FIP200 interacts with TSC1 (not TSC2) to form a complex with TSC1-TSC2, and this interaction regulates cell size and S6 kinase phosphorylation. FIP200 overexpression reduces TSC1-TSC2 complex formation; knockdown of FIP200 reduces S6K phosphorylation and cell size in a TSC1-dependent manner. Coimmunoprecipitation, RNAi knockdown, cell size measurement, Western blot The Journal of cell biology Medium 16043512
2005 FIP200 (RB1CC1) stabilizes p53 protein by increasing its half-life, reducing proteasomal degradation via a ubiquitin- and Hdm2-independent mechanism. The N-terminal 154 residues of FIP200 are sufficient for p53 interaction. FIP200 also decreases cyclin D1 protein half-life by promoting proteasome-dependent degradation, leading to G1 arrest in breast cancer cells. Coimmunoprecipitation, pulse-chase/half-life assay, flow cytometry, luciferase reporter, domain mapping Cancer research Medium 16061648
2006 FIP200 knockout in mice leads to reduced S6 kinase activation and cell size via increased TSC1-TSC2 complex function, and increased apoptosis through impaired JNK phosphorylation in response to TNFα. FIP200 interacts with ASK1 and TRAF2, regulates TRAF2-ASK1 interaction, and affects ASK1 phosphorylation. Mouse knockout, coimmunoprecipitation, kinase assays, Western blot The Journal of cell biology High 17015619
2006 RB1CC1 promotes TSC1 degradation through the ubiquitin-proteasomal pathway to maintain mTOR/S6K activity and cell size, particularly in neuromuscular cells. RNAi knockdown, Western blot, cell size measurement, proteasome inhibitor experiments International journal of molecular medicine Medium 16865226
2008 FIP200 was identified as a ULK1/2-interacting protein required for autophagosome formation. FIP200 localizes to the autophagic isolation membrane under starvation. FIP200-deficient cells exhibit abolished autophagy induction and impaired ULK1 stability and phosphorylation. Coimmunoprecipitation, immunofluorescence, conditional KO mouse embryo fibroblasts, Western blot The Journal of cell biology High 18443221
2008 FIP200 interacts with PIASy via the RING finger of PIASy and the C-terminus of FIP200. PIASy redistributes FIP200 from cytoplasm to nucleus, abolishing FIP200 regulation of TSC/S6K signaling. FIP200 and PIASy are co-recruited to the p21 promoter and cooperate to enhance p21 transcriptional activation. Coimmunoprecipitation, immunofluorescence, subcellular fractionation, ChIP, luciferase reporter, siRNA Molecular and cellular biology Medium 18285457
2009 FIP200 forms a stable ~3 MDa complex with ULK1 and Atg13 in mammalian cells. In contrast to yeast, this complex formation is not altered by nutrient conditions. mTORC1 is incorporated into the ULK1-Atg13-FIP200 complex through ULK1 in a nutrient-dependent manner and phosphorylates ULK1 and Atg13. Starvation or rapamycin causes ULK1 dephosphorylation. Coimmunoprecipitation, gel filtration, mass spectrometry, Western blot Molecular biology of the cell High 19211835
2009 FIP200 and ATG13 are required for correct localization of ULK1 to the pre-autophagosome and for ULK1 protein stability. In a de novo in vitro reconstituted reaction, FIP200 and ATG13 individually enhance ULK1 kinase activity but both are required for maximal stimulation. In vitro kinase reconstitution, coimmunoprecipitation, immunofluorescence, KO/knockdown The Journal of biological chemistry High 19258318
2009 FIP200 is essential for autophagy induction; neural-specific deletion of FIP200 in mice leads to cerebellar degeneration with accumulation of ubiquitinated protein aggregates, increased p62/SQSTM1, reduced autophagosome formation, accumulation of damaged mitochondria, and increased apoptosis with reduced JNK activation. Conditional KO mouse, electron microscopy, immunohistochemistry, Western blot, in vitro neuron culture The Journal of biological chemistry High 19940130
2011 Cytoplasmic p53 inhibits autophagy through a direct molecular interaction with RB1CC1/FIP200. A single point mutation in p53 (K382R) abolishes both its autophagy-inhibiting capacity and its ability to co-immunoprecipitate with RB1CC1/FIP200. Coimmunoprecipitation, point mutagenesis, autophagy functional assays in p53-deficient cells Cell cycle Medium 21775823
2011 RB1CC1 (nuclear) forms a complex with hSNF5 and/or p53 and activates transcription of RB1, p16, and p21 by direct binding to the RB1 promoter, suppressing tumor cell growth. Coimmunoprecipitation, ChIP, luciferase reporter, RT-PCR, flow cytometry PloS one Medium 20614030
2011 RB1CC1/FIP200 positively regulates TGF-β signaling by acting as a substrate-selective cofactor of Arkadia E3 ubiquitin ligase. RB1CC1 enhances Arkadia-mediated ubiquitination and degradation of c-Ski (but not SnoN) through direct physical interaction with c-Ski as a scaffold. Coimmunoprecipitation, ubiquitination assay, knockdown/overexpression with target gene expression readouts The Journal of biological chemistry Medium 21795712
2012 FIP200 directly interacts with ATG16L1 via a short FIP200-binding domain (FBD) in ATG16L1. This interaction connects the ULK1 complex to the ATG5 complex. The FBD is not required for ATG16L1 dimerization or ATG5 binding but is required for amino acid starvation-induced (ULK1-dependent) autophagy, while glucose deprivation-induced (ULK1-independent) autophagy is retained in FBD-deleted ATG16L1. Coimmunoprecipitation, domain deletion mutagenesis, autophagy flux assays Nature structural & molecular biology High 23262492
2013 FIP200 directly interacts with Atg16L1 in a phosphatidylinositol 3-kinase- and Atg14-independent manner. Atg16L1 deletion mutants lacking the FIP200-interacting domain are defective in proper membrane targeting to the isolation membrane, indicating FIP200 regulates both early and late events of autophagosome formation. Coimmunoprecipitation, domain deletion mutagenesis, immunofluorescence localization of Atg16L1 mutants EMBO reports High 23392225
2016 Residues 582-585 (LQFL) in FIP200 are required for interaction with Atg13. Mutation of these residues to AAAA (FIP200-4A) abolishes canonical autophagy in vitro and in vivo (knock-in mouse). The FIP200-4A knock-in mouse demonstrates that nonautophagic FIP200 functions (including protection from TNFα-induced apoptosis) are sufficient for embryogenesis, but autophagy-dependent FIP200 function is required for neonatal survival and tumor growth. Point mutagenesis, conditional KO and knock-in mouse models, autophagy flux assays, co-IP Genes & development High 27013233
2019 The C-terminal region (CTR) of FIP200 contains a dimeric globular domain called the 'Claw', which directly interacts with disordered residues 326-380 of p62/SQSTM1. The interaction is mediated by a positively charged pocket in the Claw, is enhanced by p62 phosphorylation, is mutually exclusive with p62-LC3B binding, promotes degradation of ubiquitinated cargo, and slows phase separation of ubiquitinated proteins by p62 in reconstituted systems. Crystal structure determination, in vitro binding/pulldown, reconstituted phase separation assay, mutagenesis, functional cargo degradation assay Molecular cell High 30853400
2020 The N-terminal 640 residues (NTD) of FIP200 interact with the C-terminal IDR of ATG13. FIP200 is a dimer, while single copies of ULK1, ATG13, and ATG101 are present in the complex. In the presence of ATG13, the FIP200 NTD adopts a C-shaped conformation ~20 nm across. The FIP200 coiled coil projects away from the crescent-shaped NTD dimer and mediates membrane and NDP52 binding. HDX-MS, negative stain EM, cryo-EM, multiangle light scattering, mutagenesis The Journal of cell biology / eLife High 32516362 32773036
2020 NDP52 allosterically stimulates membrane binding by the ULK1 complex by promoting a more dynamic conformation of the membrane-binding portion of the FIP200 coiled coil. Giant unilamellar vesicle reconstitution confirmed NDP52-triggered membrane recruitment of the ULK1 complex. The membrane and NDP52 binding sites map to unique regions of the FIP200 coiled coil. HDX-MS, GUV reconstitution, electron microscopy eLife High 32773036
2020 In the absence of LC3 lipidation machinery (ATG7KO), FIP200 is still required for NBR1 flux. TAX1BP1 clusters FIP200 around NBR1 cargo and induces local autophagosome formation, replacing the requirement for lipidated LC3. TAX1BP1 recruitment to NBR1 puncta occurs via a ubiquitin-independent mode. Genome-wide CRISPR screens, KO cells, immunofluorescence, autophagy flux assays The EMBO journal High 33226137
2020 CALCOCO2/NDP52 interacts with RB1CC1 to initiate de novo biogenesis of autophagic membranes on ubiquitin-coated damaged mitochondria, defining the CALCOCO2-RB1CC1 axis as one of two axes (the other being OPTN-ATG9A) for PINK1/PRKN-mediated mitophagy. Coimmunoprecipitation, mitophagy assays, KO cell lines Autophagy Medium 32892694
2021 Crystal structures of the FIP200 Claw domain in complex with phosphorylated CCPG1 and Optineurin reveal that phosphorylation in their FIP200-binding regions enhances interactions with the FIP200 Claw. A consensus FIP200 Claw-binding motif was defined, present in multiple autophagy receptors within or near their LIR regions. Crystal structure determination, in vitro binding assays, phosphorylation site mutagenesis Nature communications High 33692357
2021 FIP200 controls the TBK1 activation threshold at SQSTM1/p62-positive condensates. In the absence of FIP200 or when FIP200 cannot bind TAX1BP1, TBK1 activation is strongly increased at p62 condensates, where TBK1 phosphorylates SQSTM1/p62 at Ser403. KO cells, Western blot, immunofluorescence, phosphorylation assays Scientific reports Medium 34226595
2022 CREBBP acetyltransferase acetylates RB1CC1 at multiple lysine residues, with K276 as the major site. K276 acetylation by CREBBP reduces ubiquitination of RB1CC1 at the same site to inhibit its ubiquitin-dependent proteasomal degradation. The N-terminal IDR of RB1CC1 can undergo liquid-liquid phase separation in vitro and drives RB1CC1 puncta formation in cells. Both K276 acetylation and the IDR are required for canonical autophagy function. Mass spectrometry, mutagenesis, in vitro LLPS assay, FRAP, co-IP, cycloheximide chase Autophagy High 36394358
2022 Autophagy stimuli trigger Ca2+ transients on the outer surface of the ER membrane, controlled by EPG-4/EI24. These Ca2+ transients trigger liquid-liquid phase separation of FIP200, forming dynamic liquid-like FIP200 puncta that nucleate autophagosome initiation sites. Multiple FIP200 puncta on the ER assemble into autophagosome formation sites dependent on ER proteins VAPA/B and ATL2/3. Multi-modal SIM imaging, Ca2+ imaging, siRNA depletion, live cell imaging, phase separation analysis Cell High 36198318
2022 Upon ferroptosis induction, RB1CC1 undergoes JNK-dependent phosphorylation at Ser537 and translocates to the nucleus, where it recruits ELP3 acetyltransferase to strengthen H4K12Ac histone modifications at enhancers linked to ferroptosis-associated genes including CHCHD3. Immunofluorescence, ChIP-seq, mutagenesis of phosphorylation site, cell-derived xenograft mouse model Clinical and translational medicine Medium 35220675
2024 TAX1BP1 has two distinct binding sites for RB1CC1: the TAX1BP1 SKICH domain binds the RB1CC1 coiled coil, and the first coiled-coil domain of TAX1BP1 binds the extreme C-terminal coiled-coil and Claw region of RB1CC1. Crystal structure of the TAX1BP1 SKICH/RB1CC1 coiled-coil complex was determined. NAP1 and RB1CC1 compete for TAX1BP1 SKICH binding but the NAP1 FIR motif can stabilize a ternary TAX1BP1/NAP1/RB1CC1 complex. Crystal structure determination, in vitro binding/pulldown, competition assay, mutagenesis Proceedings of the National Academy of Sciences of the United States of America High 38437556
2016 FIP200 deletion in neural stem/progenitor cells increases Ccl5 and Cxcl10 expression (via p62 aggregate-induced NF-κB activation, independent of p53), mediating increased microglia infiltration. Activated microglia (M1 phenotype) inhibit differentiation of FIP200-null NSCs non-cell-autonomously. Blocking microglia infiltration or activation rescues differentiation defects. Conditional KO mouse, NF-κB pathway analysis, microglia depletion/blocking experiments, flow cytometry The Journal of cell biology High 28634261
2020 FIP200 suppresses TBK1-IFN signaling independently of its autophagy function by interacting with the TBK1 adaptor protein AZI2. Complete ablation or disruption of non-canonical autophagy function of FIP200 activates the AZI2/TBK1/IRF signaling axis to promote T-cell recruitment in mammary tumors. Conditional KO mouse models, co-IP of FIP200-AZI2 interaction, gene expression analysis, immune cell profiling Cancer research Medium 32580962
2016 PSCA interacts with RB1CC1 in the cytoplasm and binding of PSCA to RB1CC1 results in stabilization and nuclear translocation of RB1CC1, thereby activating cell cycle arrest and differentiation programs. Coimmunoprecipitation, immunofluorescence, nuclear/cytoplasmic fractionation Carcinogenesis Low 26785734

Source papers

Stage 0 corpus · 100 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2009 Nutrient-dependent mTORC1 association with the ULK1-Atg13-FIP200 complex required for autophagy. Molecular biology of the cell 1661 19211835
2009 ULK1.ATG13.FIP200 complex mediates mTOR signaling and is essential for autophagy. The Journal of biological chemistry 1227 19258318
2008 FIP200, a ULK-interacting protein, is required for autophagosome formation in mammalian cells. The Journal of cell biology 809 18443221
2011 Suppression of autophagy by FIP200 deletion inhibits mammary tumorigenesis. Genes & development 341 21764854
2005 Atg17 functions in cooperation with Atg1 and Atg13 in yeast autophagy. Molecular biology of the cell 285 15743910
2019 FIP200 Claw Domain Binding to p62 Promotes Autophagosome Formation at Ubiquitin Condensates. Molecular cell 277 30853400
2006 Role of FIP200 in cardiac and liver development and its regulation of TNFalpha and TSC-mTOR signaling pathways. The Journal of cell biology 197 17015619
2005 Atg17 regulates the magnitude of the autophagic response. Molecular biology of the cell 195 15901835
2010 FIP200 is required for the cell-autonomous maintenance of fetal hematopoietic stem cells. Blood 193 20716775
2013 Suppression of autophagy by FIP200 deletion leads to osteopenia in mice through the inhibition of osteoblast terminal differentiation. Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research 185 23633228
2009 Neural-specific deletion of FIP200 leads to cerebellar degeneration caused by increased neuronal death and axon degeneration. The Journal of biological chemistry 185 19940130
2009 mTORC1 phosphorylates the ULK1-mAtg13-FIP200 autophagy regulatory complex. Science signaling 183 19690328
2012 Interaction between FIP200 and ATG16L1 distinguishes ULK1 complex-dependent and -independent autophagy. Nature structural & molecular biology 182 23262492
2017 Autophagy-Independent Lysosomal Targeting Regulated by ULK1/2-FIP200 and ATG9. Cell reports 162 28877469
2013 FIP200 regulates targeting of Atg16L1 to the isolation membrane. EMBO reports 162 23392225
2013 FIP200 is required for maintenance and differentiation of postnatal neural stem cells. Nature neuroscience 146 23542691
2022 Calcium transients on the ER surface trigger liquid-liquid phase separation of FIP200 to specify autophagosome initiation sites. Cell 144 36198318
2017 Suppression of FIP200 and autophagy by tumor-derived lactate promotes naïve T cell apoptosis and affects tumor immunity. Science immunology 131 29150439
2009 Atg17 recruits Atg9 to organize the pre-autophagosomal structure. Genes to cells : devoted to molecular & cellular mechanisms 126 19371383
2011 p53 inhibits autophagy by interacting with the human ortholog of yeast Atg17, RB1CC1/FIP200. Cell cycle (Georgetown, Tex.) 117 21775823
2011 Atg13 and FIP200 act independently of Ulk1 and Ulk2 in autophagy induction. Autophagy 116 22024743
2015 Deletion of autophagy inducer RB1CC1 results in degeneration of the retinal pigment epithelium. Autophagy 115 26075877
2019 Increases in miR-124-3p in Microglial Exosomes Confer Neuroprotective Effects by Targeting FIP200-Mediated Neuronal Autophagy Following Traumatic Brain Injury. Neurochemical research 108 31190315
2002 Regulation of focal adhesion kinase by a novel protein inhibitor FIP200. Molecular biology of the cell 105 12221124
2016 The oligodendrocyte-specific antibody 'CC1' binds Quaking 7. Journal of neurochemistry 102 27454326
2020 Receptor-mediated clustering of FIP200 bypasses the role of LC3 lipidation in autophagy. The EMBO journal 100 33226137
2009 Role of ULK-FIP200 complex in mammalian autophagy: FIP200, a counterpart of yeast Atg17? Autophagy 97 18981720
2013 Autophagy deficiency by hepatic FIP200 deletion uncouples steatosis from liver injury in NAFLD. Molecular endocrinology (Baltimore, Md.) 95 23960084
2005 Identification of FIP200 interaction with the TSC1-TSC2 complex and its role in regulation of cell size control. The Journal of cell biology 83 16043512
2013 Atg29 phosphorylation regulates coordination of the Atg17-Atg31-Atg29 complex with the Atg11 scaffold during autophagy initiation. Proceedings of the National Academy of Sciences of the United States of America 77 23858448
2011 Suppression of autophagy by FIP200 deletion impairs DNA damage repair and increases cell death upon treatments with anticancer agents. Molecular cancer research : MCR 76 21807966
2005 Mechanism of cell cycle regulation by FIP200 in human breast cancer cells. Cancer research 75 16061648
2020 ULK complex organization in autophagy by a C-shaped FIP200 N-terminal domain dimer. The Journal of cell biology 73 32516362
2016 Distinct roles of autophagy-dependent and -independent functions of FIP200 revealed by generation and analysis of a mutant knock-in mouse model. Genes & development 72 27013233
2021 Phosphorylation regulates the binding of autophagy receptors to FIP200 Claw domain for selective autophagy initiation. Nature communications 70 33692357
2014 Atg17/FIP200 localizes to perilysosomal Ref(2)P aggregates and promotes autophagy by activation of Atg1 in Drosophila. Autophagy 68 24419107
2000 Suppression of Pyk2 kinase and cellular activities by FIP200. The Journal of cell biology 66 10769033
2020 The autophagy adaptor NDP52 and the FIP200 coiled-coil allosterically activate ULK1 complex membrane recruitment. eLife 62 32773036
2002 Truncating mutations of RB1CC1 in human breast cancer. Nature genetics 62 12068296
2007 FIP200, a key signaling node to coordinately regulate various cellular processes. Cellular signalling 61 18036779
2002 Identification of RB1CC1, a novel human gene that can induce RB1 in various human cells. Oncogene 61 11850849
2014 Identification of miR-133b and RB1CC1 as independent predictors for biochemical recurrence and potential therapeutic targets for prostate cancer. Clinical cancer research : an official journal of the American Association for Cancer Research 60 24610824
2016 miR-224-3p inhibits autophagy in cervical cancer cells by targeting FIP200. Scientific reports 57 27615604
2022 Tumour cells are sensitised to ferroptosis via RB1CC1-mediated transcriptional reprogramming. Clinical and translational medicine 46 35220675
2007 RB1CC1 insufficiency causes neuronal atrophy through mTOR signaling alteration and involved in the pathology of Alzheimer's diseases. Brain research 46 17706618
1989 Kupffer cells from CC1(4)-treated rat livers induce skin fibroblast and liver fat-storing cell proliferation in culture. Matrix (Stuttgart, Germany) 46 2725421
2016 MiR-20a and miR-20b negatively regulate autophagy by targeting RB1CC1/FIP200 in breast cancer cells. Life sciences 45 26829385
2013 Drosophila Fip200 is an essential regulator of autophagy that attenuates both growth and aging. Autophagy 45 23819996
1992 Glycoconjugates are stage- and position-specific cell surface molecules in the developing olfactory system, 1: The CC1 immunoreactive glycolipid defines a rostrocaudal gradient in the rat vomeronasal system. Journal of neurobiology 44 1382115
2016 The Atg17-Atg31-Atg29 Complex Coordinates with Atg11 to Recruit the Vam7 SNARE and Mediate Autophagosome-Vacuole Fusion. Current biology : CB 41 26774783
2018 RB1CC1-enhanced autophagy facilitates PSCs activation and pancreatic fibrogenesis in chronic pancreatitis. Cell death & disease 39 30237496
2020 Two different axes CALCOCO2-RB1CC1 and OPTN-ATG9A initiate PRKN-mediated mitophagy. Autophagy 38 32892694
2020 The autophagy protein, FIP200 (RB1CC1) mediates progesterone responses governing uterine receptivity and decidualization†. Biology of reproduction 37 31901086
2021 FIP200 controls the TBK1 activation threshold at SQSTM1/p62-positive condensates. Scientific reports 36 34226595
2019 miR-20a inhibits hypoxia-induced autophagy by targeting ATG5/FIP200 in colorectal cancer. Molecular carcinogenesis 35 30883936
2020 Interhelical interactions within the STIM1 CC1 domain modulate CRAC channel activation. Nature chemical biology 34 33106661
2013 Structural characterization of the Saccharomyces cerevisiae autophagy regulatory complex Atg17-Atg31-Atg29. Autophagy 34 23939028
2008 Inactivation of FIP200 leads to inflammatory skin disorder, but not tumorigenesis, in conditional knock-out mouse models. The Journal of biological chemistry 34 19106106
2006 CC1, a novel crenarchaeal DNA binding protein. Journal of bacteriology 32 17085561
2020 FIP200 Suppresses Immune Checkpoint Therapy Responses in Breast Cancers by Limiting AZI2/TBK1/IRF Signaling Independent of Its Canonical Autophagy Function. Cancer research 31 32580962
2017 Autophagy gene FIP200 in neural progenitors non-cell autonomously controls differentiation by regulating microglia. The Journal of cell biology 31 28634261
2010 RB1CC1 activates RB1 pathway and inhibits proliferation and cologenic survival in human cancer. PloS one 31 20614030
2022 Regulation of RB1CC1/FIP200 stability and autophagy function by CREBBP-mediated acetylation in an intrinsically disordered region. Autophagy 28 36394358
2019 Overexpression of miR-224-3p alleviates apoptosis from cerebral ischemia reperfusion injury by targeting FIP200. Journal of cellular biochemistry 28 31134677
2011 RB1CC1 protein positively regulates transforming growth factor-beta signaling through the modulation of Arkadia E3 ubiquitin ligase activity. The Journal of biological chemistry 28 21795712
2009 RB1CC1 activates the promoter and expression of RB1 in human cancer. International journal of cancer 28 19437535
2021 Exploring the evolution and epidemiology of European CC1-MRSA-IV: tracking a multidrug-resistant community-associated meticillin-resistant Staphylococcus aureus clone. Microbial genomics 27 34223815
2006 Neuromuscular abundance of RB1CC1 contributes to the non-proliferating enlarged cell phenotype through both RB1 maintenance and TSC1 degradation. International journal of molecular medicine 27 16865226
2011 Downregulation of FIP200 induces apoptosis of glioblastoma cells and microvascular endothelial cells by enhancing Pyk2 activity. PloS one 26 21602932
2023 [123I]CC1: A PARP-Targeting, Auger Electron-Emitting Radiopharmaceutical for Radionuclide Therapy of Cancer. Journal of nuclear medicine : official publication, Society of Nuclear Medicine 25 37770109
2014 Tumor-suppressive functions of 15-Lipoxygenase-2 and RB1CC1 in prostate cancer. Cell cycle (Georgetown, Tex.) 25 24732589
2013 CCCP-Induced LC3 lipidation depends on Atg9 whereas FIP200/Atg13 and Beclin 1/Atg14 are dispensable. Biochemical and biophysical research communications 23 23402761
2018 MiRNA-409-3p enhances cisplatin-sensitivity of ovarian cancer cells by blocking the autophagy mediated by Fip200. Oncology research 22 29295727
2008 Spatial interplay between PIASy and FIP200 in the regulation of signal transduction and transcriptional activity. Molecular and cellular biology 22 18285457
2023 METTL14 inhibits malignant progression of oral squamous cell carcinoma by targeting the autophagy-related gene RB1CC1 in an m6A-IGF2BP2-dependent manner. Clinical science (London, England : 1979) 21 37615536
2021 ZBTB28 induces autophagy by regulation of FIP200 and Bcl-XL facilitating cervical cancer cell apoptosis. Journal of experimental & clinical cancer research : CR 21 33931087
2011 FIP200, an essential component of mammalian autophagy is indispensible for fetal hematopoiesis. Autophagy 21 21088496
2010 RB1CC1 together with RB1 and p53 predicts long-term survival in Japanese breast cancer patients. PloS one 21 21203526
2024 FERONIA adjusts CC1 phosphorylation to control microtubule array behavior in response to salt stress. Science advances 20 39612333
2019 A novel multidrug-resistant PVL-negative CC1-MRSA-IV clone emerging in Ireland and Germany likely originated in South-Eastern Europe. Infection, genetics and evolution : journal of molecular epidemiology and evolutionary genetics in infectious diseases 20 30677533
2020 Protocol of a prospective, multicentre phase I study to evaluate the safety, tolerability and preliminary efficacy of the bispecific PSMAxCD3 antibody CC-1 in patients with castration-resistant prostate carcinoma. BMJ open 17 33067297
2019 Autophagosome closure by ESCRT: Vps21/RAB5-regulated ESCRT recruitment via an Atg17-Snf7 interaction. Autophagy 17 31170863
2019 Predominance of methicillin-resistant Staphylococcus aureus SCCmec type II-CC5 and SCCmec type IV-CC1/CC8 among companion animal clinical isolates in Japan: Findings from phylogenetic comparison with human clinical isolates. Journal of global antimicrobial resistance 17 31472282
2016 PSCA acts as a tumor suppressor by facilitating the nuclear translocation of RB1CC1 in esophageal squamous cell carcinoma. Carcinogenesis 17 26785734
2015 Improving transformation of Staphylococcus aureus belonging to the CC1, CC5 and CC8 clonal complexes. PloS one 17 25807379
2014 FIP200 is involved in murine pseudomonas infection by regulating HMGB1 intracellular translocation. Cellular physiology and biochemistry : international journal of experimental cellular physiology, biochemistry, and pharmacology 17 24923305
2002 Isolation, characterization and mapping of the mouse and human RB1CC1 genes. Gene 17 12095676
2022 Predominance of ST8 and CC1/spa-t1784 methicillin-resistant Staphylococcus aureus isolates in Japan and their genomic characteristics. Journal of global antimicrobial resistance 16 35092827
2022 The novel fosfomycin resistance gene fosY is present on a genomic island in CC1 methicillin-resistant Staphylococcus aureus. Emerging microbes & infections 16 35332834
2017 Comparison of the expression of TGF-β1, E-cadherin, N-cadherin, TP53, RB1CC1 and HIF-1α in oral squamous cell carcinoma and lymph node metastases of humans and mice. Oncology letters 16 29399192
2003 RB1CC1 suppresses cell cycle progression through RB1 expression in human neoplastic cells. International journal of molecular medicine 16 14533007
2022 Mapping interactions between the CRAC activation domain and CC1 regulating the activity of the ER Ca2+ sensor STIM1. The Journal of biological chemistry 15 35724962
2022 Taxifolin-3-O-glucoside from Osbeckia nepalensis Hook. mediates antihyperglycemic activity in CC1 hepatocytes and in diabetic Wistar rats via regulating AMPK/G6Pase/PEPCK signaling axis. Journal of ethnopharmacology 15 36403743
2019 How RB1CC1/FIP200 claws its way to autophagic engulfment of SQSTM1/p62-ubiquitin condensates. Autophagy 15 31066340
2024 Mechanistic insights into the interactions of TAX1BP1 with RB1CC1 and mammalian ATG8 family proteins. Proceedings of the National Academy of Sciences of the United States of America 14 38437556
2022 Circ-CUL2/microRNA-888-5p/RB1CC1 axis participates in cisplatin resistance in NSCLC via repressing cell advancement. Bioengineered 14 35068326
2021 RB1CC1 functions as a tumor-suppressing gene in renal cell carcinoma via suppression of PYK2 activity and disruption of TAZ-mediated PDL1 transcription activation. Cancer immunology, immunotherapy : CII 14 33837850
2018 IGF2-derived miR-483-3p contributes to macrosomia through regulating trophoblast proliferation by targeting RB1CC1. Molecular human reproduction 14 29939354
2016 Establishment of clival chordoma cell line MUG-CC1 and lymphoblastoid cells as a model for potential new treatment strategies. Scientific reports 14 27072875
2005 Rb1cc1 is critical for myoblast differentiation through Rb1 regulation. Virchows Archiv : an international journal of pathology 14 15968549

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