Affinage

RUBCN

Run domain Beclin-1-interacting and cysteine-rich domain-containing protein · UniProt Q92622

Length
972 aa
Mass
108.6 kDa
Annotated
2026-04-28
91 papers in source corpus 30 papers cited in narrative 30 extracted findings

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

Rubicon (RUBCN) is a multifunctional endosomal scaffold that integrates autophagy, endocytic trafficking, innate immunity, and exosome biogenesis by coupling Rab7-GTP sensing to the regulation of PI3K-III (Vps34) complexes. As a component of UVRAG–Beclin 1–Vps34 complexes on late endosomes, Rubicon suppresses autophagosome–lysosome fusion by inhibiting Vps34 kinase activity through its RUN domain, while its C-terminal RH domain binds Rab7-GTP to sequester UVRAG from the HOPS tethering complex; TBK1-mediated phosphorylation of RAB7A at Ser72 releases Rubicon to relieve this inhibition during mitophagy (PMID:19270696, PMID:20974968, PMID:21062745, PMID:32632011, PMID:38728007). Independent of canonical autophagy, Rubicon promotes phagosomal NADPH oxidase activation via p22phox interaction, dampens type I interferon signaling by blocking IRF3 dimerization and NEMO function, negatively regulates CARD9–BCL10–MALT1 inflammasome signaling, participates in NLRP3 inflammasome activation through a ZFYVE21–RNF34 endosomal complex, and recruits WIPI2d to endosomes to drive ESCRT-dependent exosome biogenesis (PMID:22423966, PMID:22423967, PMID:28468885, PMID:37225719, PMID:39174742). Rubicon protein levels are controlled transcriptionally (by FXR) and post-translationally by HECTD1-mediated K534 ubiquitination, TRIM21/ENKD1-directed K48 ubiquitination, m6A-dependent mRNA stabilization, and HUNK-mediated phosphorylation; age-dependent accumulation of Rubicon impairs autophagic capacity and contributes to organismal aging, while its loss in specific tissues disrupts adipocyte PPARγ signaling, spermatogenesis, and platelet thrombus formation (PMID:36121967, PMID:30783089, PMID:32811819, PMID:34351902, PMID:41259739).

Mechanistic history

Synthesis pass · year-by-year structured walk · 15 steps
  1. 2009 High

    Identification of Rubicon as a Beclin 1-interacting protein that specifically joins UVRAG-containing (not Atg14L-containing) PI3K-III complexes and negatively regulates autophagy maturation and endocytic trafficking established its identity as the first dedicated inhibitor of late-stage autophagy.

    Evidence Mass spectrometry, co-IP, siRNA knockdown with autophagy flux readouts, independently reported by two laboratories

    PMID:19270693 PMID:19270696

    Open questions at the time
    • No structural basis for Rubicon–Beclin 1 interaction
    • Mechanism of maturation block (fusion vs. lysosome function) unresolved
  2. 2009 High

    Demonstration that Rubicon directly reduces Vps34 lipid kinase activity linked its autophagy-suppressive function to a specific enzymatic target, establishing a biochemical mechanism rather than merely a correlative association.

    Evidence In vitro PI3K lipid kinase assay with overexpression/knockdown, replicated across two labs

    PMID:19270693 PMID:19270696

    Open questions at the time
    • Which Rubicon domain mediates kinase inhibition was unknown
    • Stoichiometry and binding mode to Vps34 undefined
  3. 2010 High

    Mapping the RUN domain as the direct Vps34-binding and kinase-inhibitory element, and the RH domain as the Rab7-GTP-binding module, resolved how Rubicon simultaneously senses endosomal identity and suppresses PI3K activity through distinct structural domains.

    Evidence Domain deletion mutagenesis, in vitro kinase assay, direct pulldown assays, functional rescue complementation

    PMID:20943950 PMID:21062745

    Open questions at the time
    • Atomic structure of either domain unresolved
    • How the two domains coordinate mechanistically unclear
  4. 2010 High

    Discovery that Rubicon sequesters UVRAG from the HOPS/C-VPS complex and that Rab7-GTP competitively releases UVRAG established a feed-forward signaling loop controlling endosome maturation, positioning Rubicon as a Rab7 effector rather than merely a passive brake.

    Evidence Co-IP, pulldown, epistasis with dominant-negative/constitutively active Rab7

    PMID:20974968

    Open questions at the time
    • Whether additional GTPases regulate this switch unknown
    • In vivo validation of the feed-forward loop lacking
  5. 2012 High

    Identification of two separable innate immune functions — promoting NADPH oxidase-driven ROS via p22phox and inhibiting CARD9–BCL10–MALT1 signaling via phosphorylation-dependent partner exchange — revealed Rubicon as a dual immune-regulatory hub operating independently of its autophagy role.

    Evidence Co-IP, ROS measurement, cytokine assays, antimicrobial activity assays, phosphorylation-dependent binding assays

    PMID:22423966 PMID:22423967

    Open questions at the time
    • Kinase(s) driving Rubicon's phosphorylation-dependent switch to CARD9 not identified
    • Domain requirements for p22phox interaction unmapped
  6. 2013 Medium

    A human disease-associated frameshift mutation deleting the C-terminal RH domain caused loss of late endosomal targeting, directly connecting structural domain function to human pathology (Salih ataxia) and confirming the RH domain as the endosomal-targeting determinant.

    Evidence Immunofluorescence colocalization of mutant vs. wild-type Rubicon

    PMID:23728897

    Open questions at the time
    • No rescue experiment with wild-type construct
    • Cerebellar pathogenesis mechanism unexplored
    • Single study without independent replication
  7. 2017 Medium

    Demonstration that Rubicon suppresses type I interferon production through two mechanisms — blocking IRF3 dimerization via its IAD and inhibiting NEMO-dependent IRF3/7 nuclear translocation — extended its immune-regulatory portfolio to antiviral defense.

    Evidence Co-IP, IRF3 dimerization assay, IFN reporter assays, viral replication readouts

    PMID:28392573 PMID:28468885

    Open questions at the time
    • Whether the IRF3 and NEMO interactions are simultaneous or context-dependent unresolved
    • Each interaction demonstrated by single lab without independent replication
  8. 2019 High

    Cross-species evidence that Rubicon accumulates with age and that its genetic removal extends lifespan and reduces age-associated pathology established Rubicon as a conserved aging modulator acting through autophagy suppression.

    Evidence Western blot/qPCR across worm, fly, and mouse tissues; RNAi lifespan extension; Rubicon KO mouse phenotyping

    PMID:30783089

    Open questions at the time
    • Mechanism driving age-dependent Rubicon accumulation unknown
    • Whether lifespan effects are entirely autophagy-dependent not formally tested
  9. 2020 High

    The 2.8 Å crystal structure of the Rubicon RH domain bound to Rab7-GTP revealed a unique four-zinc-cluster fold and a non-canonical Rab-effector binding mode, providing the first atomic framework for understanding how Rubicon senses endosomal Rab7 and how mutations disrupt this interaction.

    Evidence X-ray crystallography, site-directed mutagenesis with live-cell colocalization and autophagic flux rescue

    PMID:32632011

    Open questions at the time
    • Full-length Rubicon structure unavailable
    • How RH domain conformational change communicates to the RUN domain unknown
  10. 2020 High

    Tissue-specific KO studies revealed that Rubicon protects PPARγ coactivators SRC-1/TIF2 from autophagic degradation in adipocytes, showing that Rubicon's autophagy brake has specific physiological substrates whose loss drives metabolic pathology (fat atrophy, hepatic steatosis).

    Evidence Adipocyte-specific Rubicon KO mice, GABARAP co-IP, PPARγ activation rescue

    PMID:32811819

    Open questions at the time
    • Whether other tissues exhibit analogous substrate-specific protection unknown
    • Selectivity mechanism for SRC-1/TIF2 autophagy targeting not fully defined
  11. 2022 High

    Identification of HECTD1-mediated K534 ubiquitination as the primary proteasomal degradation signal for Rubicon established a direct post-translational mechanism controlling Rubicon protein levels, with in vivo relevance to osteoarthritis progression.

    Evidence Co-IP, ubiquitination assay, K534R mutagenesis, proteasome inhibitor, OA mouse model

    PMID:36121967

    Open questions at the time
    • Whether K534 ubiquitination is regulated by upstream signaling unknown
    • Relationship between HECTD1 and other Rubicon-degrading E3 ligases (TRIM21) unclear
  12. 2023 Medium

    Discovery of a shorter RUBCN100 isoform (lacking the RUN domain) that localizes to early endosomes and promotes Vps34 activity revealed that the RUBCN locus encodes opposing autophagy regulators, fundamentally reframing Rubicon biology from a simple inhibitor to a dual-function locus.

    Evidence Alternative translation initiation mapping, Vps34 kinase assay, B cell-specific KO

    PMID:37725663

    Open questions at the time
    • Relative expression and tissue distribution of RUBCN100 vs. RUBCN130 not systematically characterized
    • Single study without independent replication
  13. 2023 Medium

    Assembly of the ZRR complex (ZFYVE21–Rubicon–RNF34) on early endosomes, where Rubicon competitively displaces the caspase-1 pseudosubstrate Flightless I, revealed an unexpected role for Rubicon in promoting NLRP3 inflammasome activation through endosomal caspase-1 liberation.

    Evidence Proteomics of FACS-sorted inflammasomes, co-IP, ubiquitination assay, endosomal fractionation, in vivo mouse models

    PMID:37225719

    Open questions at the time
    • How ZRR complex assembly is triggered remains unknown
    • Relationship to Rubicon's CARD9-inhibitory function not reconciled
  14. 2024 High

    TBK1-mediated phosphorylation of RAB7A at Ser72 was shown to abrogate Rubicon binding and simultaneously enable Pacer recruitment, establishing a phospho-switch that toggles endosomal autophagy regulation from inhibitory (Rubicon) to permissive (Pacer) during mitophagy.

    Evidence In vitro TBK1 phosphorylation assay, structural analysis, colocalization upon mitochondrial depolarization, Pacer KO rescue

    PMID:38728007

    Open questions at the time
    • Whether other kinases besides TBK1 regulate this switch in different contexts unknown
    • Whether the switch operates in selective autophagy beyond mitophagy untested
  15. 2024 High

    Demonstration that Rubicon recruits WIPI2d to endosomes to drive ESCRT-dependent exosome biogenesis expanded Rubicon's functional scope beyond autophagy to vesicular secretion and linked age-dependent Rubicon accumulation to increased exosome-mediated senescence signaling.

    Evidence Genome-wide RNAi screen, WIPI2d interactome, live-cell imaging, small RNA sequencing of exosomes from Rubicon KO mice

    PMID:39174742

    Open questions at the time
    • How Rubicon switches between autophagy suppression and exosome biogenesis roles is unclear
    • WIPI2d recruitment mechanism at the molecular level undefined

Open questions

Synthesis pass · forward-looking unresolved questions
  • Major unresolved questions include: the full-length Rubicon structure and how its domains are allosterically coordinated; how opposing isoform functions (RUBCN130 vs. RUBCN100) are regulated tissue-specifically; the integrated logic by which Rubicon's autophagy, innate immune, and exosome functions are contextually selected; and whether Rubicon's aging-associated accumulation is a cause or consequence of declining proteostasis.
  • Full-length structure unavailable
  • Isoform-specific regulation uncharacterized across tissues
  • No unified model of context-dependent functional switching

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0060090 molecular adaptor activity 6 GO:0098772 molecular function regulator activity 3
Localization
GO:0005768 endosome 6 GO:0005764 lysosome 2 GO:0031410 cytoplasmic vesicle 1
Pathway
R-HSA-9612973 Autophagy 11 R-HSA-168256 Immune System 6 R-HSA-162582 Signal Transduction 4 R-HSA-5653656 Vesicle-mediated transport 3 R-HSA-8953854 Metabolism of RNA 1
Partners
BECN1CARD9CYBAHECTD1PIK3C3RAB7AUVRAGWIPI2
Complex memberships
UVRAG-Beclin 1-Vps34 PI3K-III complexZRR complex (ZFYVE21-Rubicon-RNF34)

Evidence

Reading pass · 30 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2009 Rubicon was identified as a novel Beclin 1-binding protein that associates exclusively with UVRAG-containing PI3K complexes (not Atg14L complexes), localizes to late endosomes/lysosomes, and negatively regulates autophagy at the maturation step as well as endocytic trafficking. Knockdown of Rubicon enhances autophagy maturation and endocytic trafficking. Mass spectrometry, co-immunoprecipitation, GFP-localization imaging, siRNA knockdown with autophagy flux readouts Nature cell biology High 19270693 19270696
2009 Rubicon reduces Vps34 (class III PI3K) lipid kinase activity, thereby downregulating autophagy. Forced expression of Rubicon results in aberrant late endosomal/lysosomal structures and impaired autophagosome maturation. Biochemical PI3K lipid kinase assay, overexpression and knockdown, immunofluorescence microscopy Nature cell biology High 19270693 19270696
2010 Rubicon acts as a Rab7 effector to control endosome maturation: Rubicon sequesters UVRAG from the C-VPS/HOPS guanine nucleotide exchange factor complex; active GTP-bound Rab7 competes for Rubicon binding and releases UVRAG to associate with HOPS, promoting further Rab7 GTP loading in a feed-forward loop. Co-immunoprecipitation, pulldown assays, functional epistasis with dominant-negative/constitutively active Rab7 constructs Proceedings of the National Academy of Sciences of the United States of America High 20974968
2010 The RUN domain of Rubicon mediates direct interaction with the PI3KC3 catalytic subunit hVps34, and this interaction is required for efficient inhibition of PI3KC3 lipid kinase activity and autophagy suppression; a RUN domain deletion mutant fails to rescue autophagy defects in Rubicon-depleted cells. Co-immunoprecipitation, in vitro PI3K lipid kinase assay, domain deletion mutant complementation The Journal of biological chemistry High 21062745
2010 Rubicon and PLEKHM1 share a C-terminal RH (Rubicon Homology) domain that directly and specifically binds Rab7, and this interaction is critical for their function in suppressing endocytic/autophagic trafficking. Rubicon uniquely also binds PI3-kinase simultaneously via this domain. Database homology search, in vitro pulldown, direct binding assays, functional mutant analysis Molecular biology of the cell High 20943950
2012 Upon microbial infection or TLR2 activation, Rubicon interacts with the p22phox subunit of the NADPH oxidase complex and facilitates phagosomal trafficking of the NADPH oxidase to induce a reactive oxygen species burst and inflammatory cytokine production. This function is genetically separable from Rubicon's role in autophagy. Co-immunoprecipitation, overexpression/knockdown with ROS measurement, cytokine assays, antimicrobial activity assays Cell host & microbe High 22423966
2012 Rubicon acts as a feedback inhibitor of CARD9-BCL10-MALT1 (CBM) complex signaling: upon Dectin-1 or RIG-I activation, Rubicon dynamically exchanges binding from 14-3-3β to CARD9 in a phosphorylation-dependent manner, disassembling the CBM complex and terminating PRR-induced cytokine production. Co-immunoprecipitation, phosphorylation-dependent binding assay, cytokine production measurement, genetic epistasis Cell host & microbe High 22423967
2013 KSHV K7 protein interacts with Rubicon and inhibits autophagosome maturation by blocking Vps34 enzymatic activity. Co-immunoprecipitation, Vps34 kinase assay, autophagy flux analysis Journal of virology Medium 24027317
2013 A loss-of-function mutation in RUBCN (frameshift deleting the C-terminal RH/diacylglycerol binding-like domain) causes the Salih ataxia mutant protein to lose its normal late endosomal localization (normally colocalizing with Rab7 and LAMP1), distributing diffusely in the cytosol, confirming the RH domain is required for endosomal targeting. Immunofluorescence colocalization in cultured cells expressing mutant vs. wild-type Rubicon Cerebellum (London, England) Medium 23728897
2017 Rubicon negatively regulates antiviral type I interferon signaling by directly interacting with the IRF association domain (IAD) of IRF3, inhibiting IRF3 dimerization and thus blocking IFN-mediated antiviral responses. Co-immunoprecipitation, IRF3 dimerization assay, knockdown/overexpression with IFN reporter assays and viral replication readouts Journal of virology Medium 28468885
2017 Rubicon binds to NEMO (NF-κB essential modulator), leading to inhibition of type-I interferon production by suppressing IRF3/IRF7 nuclear translocation, thereby promoting viral replication. Co-immunoprecipitation, nuclear translocation assay, IFN reporter assay, overexpression/knockdown with viral replication readout Cellular & molecular immunology Medium 28392573
2019 Rubicon expression increases in aged worm, fly, and mouse tissues, and this age-dependent increase impairs autophagic activity. Knockdown of Rubicon extends lifespan in worms and flies and reduces age-associated pathology (interstitial fibrosis, α-synuclein accumulation) in mice. Western blot/qPCR for expression, RNAi knockdown with lifespan and phenotypic readouts across multiple organisms, Rubicon KO mouse analysis Nature communications High 30783089
2019 HUNK kinase phosphorylates Rubicon, and this phosphorylation inhibits Rubicon's autophagy-suppressive function, thereby promoting autophagy. Co-immunoprecipitation, in vitro kinase assay, LC3B immunofluorescence and immunoblotting International journal of molecular sciences Medium 31752345
2020 Crystal structure (2.8 Å) of the Rubicon RH domain in complex with Rab7-GTP revealed the RH domain fold built around four zinc clusters; Rab7 switch regions insert into pockets on the RH domain surface in a mode distinct from other Rab-effector complexes. Rubicon residues at the dimer interface are required for colocalization with Rab7 in living cells, and mutation of Rab7-binding residues in RH restores autophagic flux in the presence of overexpressed Rubicon. X-ray crystallography, mutagenesis, live-cell colocalization, autophagic flux assay Proceedings of the National Academy of Sciences of the United States of America High 32632011
2020 Upregulation of Rubicon during myocardial ischemia/reperfusion attenuates autophagic flux and triggers accumulation of autophagosomes leading to autosis (a morphologically distinct form of cell death). Genetic downregulation of Rubicon inhibited autosis and reduced I/R injury. Mouse I/R model, Rubicon genetic knockdown/overexpression, autophagic flux assay, histological assessment of autosis markers The Journal of clinical investigation Medium 32364533
2020 FXR (farnesoid X receptor) directly binds the Rubicon promoter and transcriptionally induces Rubicon expression in cholestasis; FXR-mediated Rubicon induction inhibits autophagosome-lysosome fusion, impairing autophagic flux. Genetic inhibition of Rubicon reverses bile acid-induced autophagy impairment. ChIP-seq, luciferase promoter assay, Rubicon siRNA knockdown with autophagic flux readouts Journal of hepatology Medium 32001325
2020 CARD9 interacts directly with Rubicon and enhances UVRAG-Beclin1-PI3KC3 interaction and UVRAG-Vps16-mediated Rab7 activation to promote autophagosome formation, maturation, and endocytosis. Rubicon siRNA knockdown abrogated the protective effect of CARD9 in cardiomyocytes. Co-immunoprecipitation, siRNA knockdown epistasis, autophagic flux assay, Rab7 activation assay Basic research in cardiology Medium 32248306
2020 In aged adipocytes, Rubicon levels decline, leading to excess autophagy that degrades SRC-1 (NCOA1) and TIF2 (NCOA2), coactivators of PPARγ, causing fat atrophy and hepatic lipid accumulation. SRC-1 and TIF2 are degraded by autophagy through binding to GABARAP family proteins. Adipocyte-specific Rubicon KO mice, autophagy flux assays, co-immunoprecipitation for GABARAP binding, PPARγ activation rescue Nature communications High 32811819
2021 METTL3 directly binds Rubicon mRNA and mediates m6A modification; YTHDF1 interacts with m6A-marked Rubicon mRNA and promotes its stability, increasing Rubicon protein levels and thereby inhibiting autophagosome-lysosome fusion in NAFLD. m6A methylation profiling, RIP (RNA immunoprecipitation), siRNA knockdown, autophagic flux assay Molecular therapy Medium 34547464
2021 Rubicon prevents autophagic degradation of GATA4 (a transcription factor essential for Sertoli cell function) in the testis. Rubicon knockout in Sertoli cells promotes GATA4 degradation via autophagy, impairing spermatogenesis and germline stem cell maintenance. Sertoli cell-specific Rubicon KO mice, autophagy flux assay, GATA4 protein level measurement, spermatogenesis phenotyping PLoS genetics Medium 34351902
2022 HECTD1, an E3 ubiquitin ligase, binds Rubicon and ubiquitinates it at lysine residue 534, targeting Rubicon for proteasomal degradation. HECTD1-mediated Rubicon degradation promotes chondrocyte autophagy and mitigates OA progression. Co-immunoprecipitation, ubiquitination assay, site-directed mutagenesis (K534), proteasome inhibitor treatment, in vivo OA mouse model Arthritis & rheumatology High 36121967
2022 Rubicon regulates beta-1 adrenergic receptor (β1AR) recycling in cardiomyocytes: Rubicon knockdown accelerates β1AR downregulation by inhibiting receptor recycling, and cardiomyocyte-specific Rubicon-deficient mice show impaired β1 adrenergic signaling and heart failure under pressure overload. Cardiomyocyte-specific KO mice, transverse aortic constriction, receptor recycling assay in neonatal rat cardiomyocytes with Rubicon knockdown Scientific reports Medium 34996972
2022 Fasting causes autophagic degradation of Rubicon itself in adipocytes, serving as a feedforward mechanism for autophagy induction; Rubicon loss promotes autophagic degradation of NCOA1/SRC-1 and NCOA2/TIF2 coactivators of PPARγ, reducing adipogenic gene expression and driving fat mobilization. Adipose-specific rubcn-KO mice, fasting experiments, autophagic flux assays, mRNA expression analysis Autophagy Medium 35282767
2023 RUBCN100, a shorter isoform of Rubicon lacking the RUN domain, promotes VPS34 activity and autophagy and localizes to early endosomes, while the full-length RUBCN130 localizes to late endosomes/lysosomes and suppresses VPS34 activity via its RUN domain; specific deficiency of RUBCN130 in B cells enhances autophagy and promotes memory B cell generation. Isoform characterization by alternative translation initiation mapping, VPS34 kinase assay, B cell-specific KO, autophagy flux assay Science signaling Medium 37725663
2023 ZFYVE21, a Rab5 effector, forms a complex with Rubicon and RNF34 (ZRR complex) on early endosomes. Rubicon within this complex competitively disrupts inhibitory associations between caspase-1 and its pseudosubstrate Flightless I (FliI), while RNF34 ubiquitinates and degradatively removes FliI, increasing endosome-associated caspase-1 available for activation, thereby promoting NLRP3 inflammasome activity. Proteomics of FACS-sorted inflammasomes, co-immunoprecipitation, ubiquitination assay, endosomal fractionation, mouse in vivo models Nature communications Medium 37225719
2024 Rubicon recruits WIPI2d to endosomes to promote exosome biogenesis; WIPI2d interactome analysis identified ESCRT components required for intraluminal vesicle formation. Rubicon is required for age-dependent increases in exosome release and determines the fate of exosomal microRNAs associated with senescence. Comprehensive RNAi screen, interactome analysis, live-cell imaging, small RNA sequencing of serum exosomes from Rubicon KO mice Nature cell biology High 39174742
2024 TBK1-mediated phosphorylation of RAB7A at Ser72 abrogates Rubicon:RAB7A binding (demonstrated by in vitro phosphorylation assay), serving as a molecular switch that relieves Rubicon inhibition of autophagy during mitophagy. Simultaneously, phospho-RAB7A recruits Pacer (a positive autophagy regulator with a complementary basic triad in its RH domain) to promote Parkin-dependent mitophagy. In vitro TBK1 phosphorylation assay, structural analysis, co-localization in cells with mitochondrial depolarization, Pacer KO rescue experiments The Journal of cell biology High 38728007
2022 DJ-1 binds to Rubicon, resulting in Rubicon degradation, decreased LC3-associated phagocytosis (LAP), and impaired bacterial clearance; DJ-1 deficiency promotes Rubicon complexing with Beclin-1 and UVRAG, facilitating autophagolysosome assembly decorated with LC3. Co-immunoprecipitation in bone marrow macrophages, bacterial clearance assays, LC3 imaging, in vivo survival experiments Cell death and differentiation Medium 35641782
2025 ENKD1 interacts with E3 ubiquitin ligase TRIM21, which mediates K48-linked polyubiquitination and degradation of RUBCN, thereby dampening RUBCN's role in LC3-associated phagocytosis (LAP) and antibacterial immunity. Co-immunoprecipitation, ubiquitination assay (K48-linkage specific), ENKD1/TRIM21/RUBCN knockdown with LAP and bacterial clearance readouts, in vivo mouse infection models Proceedings of the National Academy of Sciences of the United States of America Medium 41187080
2026 In platelets, Rubicon interacts with Bruton's tyrosine kinase (Btk) to inhibit GPVI-mediated thrombus formation, while also preventing αIIbβ3-mediated selective autophagy and degradation of Btk to stabilize platelet thrombi. Platelet-specific Rubicon deficiency impairs phosphatidylserine exposure and collagen binding under high shear, indicating an autophagy-independent role in thrombosis. Platelet/megakaryocyte-specific Rubicon KO mice, FeCl3 carotid artery injury model, microfluidics assay, co-immunoprecipitation, PS exposure assay Blood advances Medium 41259739

Source papers

Stage 0 corpus · 91 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2009 Two Beclin 1-binding proteins, Atg14L and Rubicon, reciprocally regulate autophagy at different stages. Nature cell biology 984 19270696
2009 Distinct regulation of autophagic activity by Atg14L and Rubicon associated with Beclin 1-phosphatidylinositol-3-kinase complex. Nature cell biology 815 19270693
2016 Rubicon inhibits autophagy and accelerates hepatocyte apoptosis and lipid accumulation in nonalcoholic fatty liver disease in mice. Hepatology (Baltimore, Md.) 293 27637015
2010 Rubicon controls endosome maturation as a Rab7 effector. Proceedings of the National Academy of Sciences of the United States of America 197 20974968
2019 Suppression of autophagic activity by Rubicon is a signature of aging. Nature communications 164 30783089
2000 Embryo implantation and GnRH antagonists: embryo implantation: the Rubicon for GnRH antagonists. Human reproduction (Oxford, England) 138 10831542
2012 Autophagy protein Rubicon mediates phagocytic NADPH oxidase activation in response to microbial infection or TLR stimulation. Cell host & microbe 134 22423966
2010 Rubicon and PLEKHM1 negatively regulate the endocytic/autophagic pathway via a novel Rab7-binding domain. Molecular biology of the cell 129 20943950
2020 Upregulation of Rubicon promotes autosis during myocardial ischemia/reperfusion injury. The Journal of clinical investigation 123 32364533
2010 The RUN domain of rubicon is important for hVps34 binding, lipid kinase inhibition, and autophagy suppression. The Journal of biological chemistry 114 21062745
2015 HCV induces the expression of Rubicon and UVRAG to temporally regulate the maturation of autophagosomes and viral replication. PLoS pathogens 109 25807108
2021 METTL3-m6A-Rubicon axis inhibits autophagy in nonalcoholic fatty liver disease. Molecular therapy : the journal of the American Society of Gene Therapy 99 34547464
2012 The autophagy regulator Rubicon is a feedback inhibitor of CARD9-mediated host innate immunity. Cell host & microbe 92 22423967
2007 Bridging the Rubicon: phylogenetic analysis reveals repeated colonizations of marine and fresh waters by thalassiosiroid diatoms. Molecular phylogenetics and evolution 86 17553708
2020 CARD9 promotes autophagy in cardiomyocytes in myocardial ischemia/reperfusion injury via interacting with Rubicon directly. Basic research in cardiology 83 32248306
2020 Age-dependent loss of adipose Rubicon promotes metabolic disorders via excess autophagy. Nature communications 72 32811819
2013 Kaposi's sarcoma-associated herpesvirus K7 modulates Rubicon-mediated inhibition of autophagosome maturation. Journal of virology 70 24027317
2002 Rubicon Genomics, Inc. Pharmacogenomics 62 12164778
2020 Podocyte EGFR Inhibits Autophagy Through Upregulation of Rubicon in Type 2 Diabetic Nephropathy. Diabetes 60 33239448
2020 FXR-dependent Rubicon induction impairs autophagy in models of human cholestasis. Journal of hepatology 59 32001325
2017 RUBCN/rubicon and EGFR regulate lysosomal degradative processes in the retinal pigment epithelium (RPE) of the eye. Autophagy 57 28933590
2023 HECTD1-Mediated Ubiquitination and Degradation of Rubicon Regulates Autophagy and Osteoarthritis Pathogenesis. Arthritis & rheumatology (Hoboken, N.J.) 45 36121967
2022 LC3-associated endocytosis and the functions of Rubicon and ATG16L1. Science advances 42 36288306
2017 Inducible Rubicon facilitates viral replication by antagonizing interferon production. Cellular & molecular immunology 38 28392573
2009 Binding Rubicon to cross the Rubicon. Autophagy 38 19550146
2010 Rundataxin, a novel protein with RUN and diacylglycerol binding domains, is mutant in a new recessive ataxia. Brain : a journal of neurology 37 20826435
2015 Rubicon swaps autophagy for LAP. Nature cell biology 36 26123110
2017 Rubicon Modulates Antiviral Type I Interferon (IFN) Signaling by Targeting IFN Regulatory Factor 3 Dimerization. Journal of virology 34 28468885
2020 Metabolic effects of RUBCN/Rubicon deficiency in kidney proximal tubular epithelial cells. Autophagy 31 31944172
2003 Nutrigenomics: the Rubicon of molecular nutrition. Journal of the American Dietetic Association 31 14666500
2022 Loss of RUBCN/rubicon in adipocytes mediates the upregulation of autophagy to promote the fasting response. Autophagy 28 35282767
2020 Structural basis for autophagy inhibition by the human Rubicon-Rab7 complex. Proceedings of the National Academy of Sciences of the United States of America 28 32632011
2015 Rubicon deficiency enhances cardiac autophagy and protects mice from lipopolysaccharide-induced lethality and reduction in stroke volume. Journal of cardiovascular pharmacology 28 25502307
2024 The Rubicon-WIPI axis regulates exosome biogenesis during ageing. Nature cell biology 23 39174742
2021 Rubicon prevents autophagic degradation of GATA4 to promote Sertoli cell function. PLoS genetics 22 34351902
2019 RUBCNL/Pacer and RUBCN/Rubicon in regulation of autolysosome formation and lipid metabolism. Autophagy 22 30894088
2019 Loss of Rubicon ameliorates doxorubicin-induced cardiotoxicity through enhancement of mitochondrial quality. International journal of cardiology 22 31439425
2024 A RAB7A phosphoswitch coordinates Rubicon Homology protein regulation of Parkin-dependent mitophagy. The Journal of cell biology 21 38728007
2021 The roles of the inhibitory autophagy regulator Rubicon in the heart: A new therapeutic target to prevent cardiac cell death. Experimental & molecular medicine 21 33854187
2019 Rubicon-Dependent Lc3 Recruitment to Salmonella-Containing Phagosomes Is a Host Defense Mechanism Triggered Independently From Major Bacterial Virulence Factors. Frontiers in cellular and infection microbiology 21 31428591
2022 Rubicon promotes the M2 polarization of Kupffer cells via LC3-associated phagocytosis-mediated clearance to improve liver transplantation. Cellular immunology 20 35700602
2020 Crossing the Vacuolar Rubicon: Structural Insights into Effector Protein Trafficking in Apicomplexan Parasites. Microorganisms 20 32521667
2020 Hepatitis C virus enhances Rubicon expression, leading to autophagy inhibition and intracellular innate immune activation. Scientific reports 20 32943718
2013 The Salih ataxia mutation impairs Rubicon endosomal localization. Cerebellum (London, England) 19 23728897
2016 Peptide inhibition of p22phox and Rubicon interaction as a therapeutic strategy for septic shock. Biomaterials 18 27267627
2022 Rubicon in Metabolic Diseases and Ageing. Frontiers in cell and developmental biology 16 35083223
2020 Ancient founder mutation in RUBCN: a second unrelated family confirms Salih ataxia (SCAR15). BMC neurology 16 32450808
2021 Acanthopanax senticosus Harms extract causes G0/G1 cell cycle arrest and autophagy via inhibition of Rubicon in human liver cancer cells. Oncology reports 15 33650674
2019 HUNK Phosphorylates Rubicon to Support Autophagy. International journal of molecular sciences 15 31752345
2016 c-Jun N-terminal kinase-mediated Rubicon expression enhances hepatocyte lipoapoptosis and promotes hepatocyte ballooning. World journal of gastroenterology 15 27605885
2024 Lipid Nanoparticle-Mediated Delivery of CRISPR-Cas9 Against Rubicon Ameliorates NAFLD by Modulating CD36 Along with Glycerophospholipid Metabolism. Advanced science (Weinheim, Baden-Wurttemberg, Germany) 14 38894572
2022 A Combination therapy using an mTOR inhibitor and Honokiol effectively induces autophagy through the modulation of AXL and Rubicon in renal cancer cells and restricts renal tumor growth following organ transplantation. Carcinogenesis 12 34965300
2024 RUBICON: a framework for designing efficient deep learning-based genomic basecallers. Genome biology 11 38365730
2023 CX3CL1 represses autophagy via CX3CR1/ CaMKIIδ/HDAC4/Rubicon axis and exacerbates chronic intermittent hypoxia induced Kupffer cell apoptosis. Cellular signalling 11 37640194
2022 Rubicon promotes rather than restricts murine lupus and is not required for LC3-associated phagocytosis. JCI insight 10 35192551
2022 Inhibition of interaction between ROCK1 and Rubicon restores autophagy in endothelial cells and attenuates brain injury after prolonged ischemia. Journal of neurochemistry 8 36334306
2016 Protein trafficking in apicomplexan parasites: crossing the vacuolar Rubicon. Current opinion in microbiology 8 27155394
2021 Mito-TIPTP Increases Mitochondrial Function by Repressing the Rubicon-p22phox Interaction in Colitis-Induced Mice. Antioxidants (Basel, Switzerland) 7 34943057
2022 Rubicon-deficiency sensitizes mice to mixed lineage kinase domain-like (MLKL)-mediated kidney ischemia-reperfusion injury. Cell death & disease 6 35288534
2020 Rubicon in pancreatic beta cells plays a limited role in maintaining glucose homeostasis following increased insulin resistance. Endocrine journal 6 32669482
2012 Crossing the Rubicon: new roads lead to host defense. Cell host & microbe 6 22423961
2025 Rubicon, a Key Molecule for Oxidative Stress-Mediated DNA Damage, in Ovarian Granulosa Cells. Antioxidants (Basel, Switzerland) 5 40298803
2024 The marine-derived compound TAG alleviates Parkinson's disease by restoring RUBCN-mediated lipid metabolism homeostasis. Acta pharmacologica Sinica 5 38538717
2023 A ZFYVE21-Rubicon-RNF34 signaling complex promotes endosome-associated inflammasome activity in endothelial cells. Nature communications 5 37225719
2023 Reduction in Rubicon by cigarette smoke is associated with impaired phagocytosis and occurs through lysosomal degradation pathway. Clinical and experimental medicine 5 37310658
2023 Opposing roles of RUBCN isoforms in autophagy and memory B cell generation. Science signaling 5 37725663
2022 Rubicon-regulated beta-1 adrenergic receptor recycling protects the heart from pressure overload. Scientific reports 5 34996972
2022 DJ-1 binds to Rubicon to Impair LC-3 Associated Phagocytosis. Cell death and differentiation 5 35641782
2022 Neuronal Rubicon Represses Extracellular APP/Amyloid β Deposition in Alzheimer's Disease. Cells 5 35740989
2022 Clinical application of RUBCN/SESN2 mediated inhibition of autophagy as biomarkers of diabetic kidney disease. Molecular medicine (Cambridge, Mass.) 5 36476132
2025 SuoquanYishen formula improves renal cellular senescence by inhibiting YTHDF1-Rubicon axis to promote autophagy in diabetic kidney disease. Frontiers in pharmacology 4 40371338
2025 Interplay of Oxidative Stress, Autophagy, and Rubicon in Ovarian Follicle Dynamics: Orchestrating Ovarian Aging. Antioxidants (Basel, Switzerland) 4 40867818
2025 Rubicon siRNA-encapsulated liver-targeting nanoliposome is a promising therapeutic for non-alcoholic fatty liver disease. International journal of pharmaceutics 3 39880145
2024 All-trans retinoic acid induces lipophagy through the activation of the AMPK-Beclin1 signaling pathway and reduces Rubicon expression in adipocytes. The Journal of nutritional biochemistry 3 38295886
2024 Rubicon regulates exosome secretion via the non-autophagic pathway. Autophagy 3 39667388
2024 Circulating autophagy regulator Rubicon is linked to increased myocardial infarction risk. Journal of molecular and cellular cardiology plus 3 39802263
2024 Plasma levels of autophagy regulator Rubicon are inversely associated with acute coronary syndrome. Frontiers in cardiovascular medicine 2 38250026
2023 Crossing the Solubility Rubicon: 15-Crown-5 Facilitates the Preparation of Water-Soluble Sulfo-NHS Esters in Organic Solvents. Bioconjugate chemistry 2 38086083
2021 Dataset on the effect of Rubicon overexpression on polyglutamine-induced locomotor dysfunction in Drosophila. Data in brief 2 34189208
2026 Role of Rubicon in platelets: a promoter of thrombosis but not an autophagy repressor. Blood advances 1 41259739
2025 [Advances in the study of viruses inhibiting the production of advanced autophagy or interferon through Rubicon to achieve innate immune escape]. Xi bao yu fen zi mian yi xue za zhi = Chinese journal of cellular and molecular immunology 1 39799430
2024 A second RUBCN variant associated with epileptic encephalopathy and neurodevelopmental delay. American journal of medical genetics. Part A 1 39520129
2026 Platelet Rubicon Bidirectional Regulation of GPVI and Integrin αIIbβ3 Signaling Mitigates Stroke Infarction Without Compromising Hemostasis. Advanced science (Weinheim, Baden-Wurttemberg, Germany) 0 41566765
2026 Rubicon modulates neuroimmune responses following traumatic brain injury. bioRxiv : the preprint server for biology 0 41867877
2025 MAB_0676c-induced enhanced IL-10 production inhibits the autophagic flux via the MTOR/RUBCN pathway. Virulence 0 40641107
2025 Salvianic acid A promotes osteogenic differentiation of bone marrow mesenchymal stem cells in senile osteoporosis through bromodomain-containing protein 4/Ariadne RBR E3 ubiquitin-protein ligase 1/Rubicon axis. Journal of traditional and complementary medicine 0 40677544
2025 ENKD1 attenuates antibacterial immunity by facilitating TRIM21-mediated RUBCN degradation to suppress LC3-associated phagocytosis. Proceedings of the National Academy of Sciences of the United States of America 0 41187080
2025 Neoadjuvant chemoimmunotherapy or chemoradiotherapy in stage III non-small cell lung cancer: crossing the Rubicon? Chinese clinical oncology 0 41208422
2025 The monkeypox virus suppresses autophagy by modulating Rubicon expression. Cell death discovery 0 41436430
2024 All-trans retinoic acid induces lipophagy by reducing Rubicon in Hepa1c1c7 cells. Journal of lipid research 0 39032560
2024 WSSV induces Rubicon expression to regulate innate immune response in Penaeus vannamei. Fish & shellfish immunology 0 39571631