Affinage

CAVIN1

Caveolae-associated protein 1 · UniProt Q6NZI2

Length
390 aa
Mass
43.5 kDa
Annotated
2026-04-28
100 papers in source corpus 34 papers cited in narrative 34 extracted findings

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

CAVIN1 (PTRF) is a multifunctional scaffolding protein essential for caveola biogenesis and ribosomal RNA transcription, with additional signaling roles that are dynamically regulated by its redistribution between the plasma membrane, cytosol, and nucleus. CAVIN1 forms flexible polyhedral coat lattices on membranes through coiled-coil-mediated oligomerization and PI(4,5)P2-dependent membrane insertion, stabilizing caveolin oligomers and preventing their lysosomal degradation; loss of CAVIN1 abolishes morphologically identifiable caveolae and reduces caveolin protein levels in all tissues examined (PMID:18191225, PMID:18840361, PMID:27834731, PMID:35696574). In the nucleus, CAVIN1 dissociates paused RNA Polymerase I ternary complexes by interacting with TTF-I, Pol I, and nascent pre-rRNA, thereby promoting transcript release and rDNA reinitiation to augment ribosomal RNA synthesis (PMID:9582279, PMID:11139612, PMID:27528195). Upon caveolar disassembly triggered by mechanical, metabolic, or oxidative stimuli, released CAVIN1 translocates to cytosol or nucleus where it facilitates NRF2 degradation to regulate ferroptosis susceptibility, remodels focal adhesions via paxillin interaction, competes with BMPR2 for caveolin-1 scaffolding domain binding to modulate BMP/Smad signaling, controls hERG channel membrane dynamics in cardiomyocytes, and anchors SOCS3 at caveolae to inhibit cytokine signaling (PMID:36858041, PMID:31126986, PMID:38182755, PMID:38682330, PMID:29330478). Loss-of-function mutations in CAVIN1 cause a congenital generalized lipodystrophy with muscular dystrophy due to secondary deficiency and mislocalization of all three caveolin isoforms (PMID:19726876, PMID:20300641).

Mechanistic history

Synthesis pass · year-by-year structured walk · 13 steps
  1. 1998 High

    The molecular function of PTRF was established: it dissociates paused RNA Polymerase I ternary complexes by interacting with TTF-I, Pol I, and the 3′ end of nascent pre-rRNA, resolving how rDNA transcription termination is completed.

    Evidence In vitro transcription release assay with recombinant PTRF and RNA-binding mutants

    PMID:9582279

    Open questions at the time
    • In vivo relevance of transcript release not yet shown
    • Structural basis of PTRF–Pol I interaction unknown
    • Post-translational regulation of this activity not addressed
  2. 1999 High

    The specificity of PTRF-mediated Pol I release was defined: PTRF acts only on termination-factor-paused complexes (TTF-I/Reb1p) and cannot release Pol I stalled by heterologous blocks, establishing it as a termination-coupled factor rather than a general release factor.

    Evidence In vitro transcription with immobilized templates and cross-species (mouse/yeast) termination factor comparison

    PMID:10589839

    Open questions at the time
    • Whether PTRF is required for all Pol I termination events in vivo unknown
    • Mechanism of specificity (direct recognition of TTF-I vs. paused complex conformation) unresolved
  3. 2001 High

    PTRF was shown to facilitate Pol I reinitiation after transcript release, linking its activity to augmented rRNA synthesis rather than merely termination; phosphorylation was identified as a regulatory mechanism governing active vs. inactive PTRF pools.

    Evidence Multiple-round in vitro transcription in a PTRF-depleted reconstituted system with phosphorylation analysis

    PMID:11139612

    Open questions at the time
    • Identity of kinases/phosphatases regulating PTRF unknown
    • Physiological stimuli controlling PTRF phosphorylation not identified
  4. 2004 High

    PTRF was unexpectedly identified as a major cytosolic coat protein of caveolae in adipocytes, revealing a second subcellular site of action; specific phosphorylation sites and calpain-cleavage sites were mapped, suggesting regulated proteolytic processing.

    Evidence Vectorial proteomics with nanospray-TOF MS on sealed caveolar vesicles from human adipocytes, confocal co-localization with caveolin

    PMID:15242332

    Open questions at the time
    • Functional role of PTRF at caveolae not yet demonstrated
    • Significance of calpain cleavage for PTRF function unknown
  5. 2008 High

    CAVIN1 was established as essential and sufficient for caveola biogenesis: its loss abolishes caveolae in all tissues, causes caveolin mislocalization and lysosomal degradation (despite normal mRNA), and its re-expression rescues caveolae in caveola-deficient cells — fundamentally redefining caveola assembly as requiring a coat protein beyond caveolins alone.

    Evidence siRNA knockdown and ectopic expression in PC3 cells, FRAP, EM; global Cavin1 knockout mice with EM, immunoblotting, and qRT-PCR

    PMID:18191225 PMID:18840361

    Open questions at the time
    • Molecular mechanism of caveolin stabilization by CAVIN1 unknown
    • Whether CAVIN1 directly contacts caveolins or acts indirectly unresolved
    • Stoichiometry of coat complex undetermined
  6. 2009 High

    Human loss-of-function PTRF mutations were shown to cause congenital generalized lipodystrophy with muscular dystrophy through secondary deficiency and mislocalization of all three caveolins, confirming the caveola-biogenesis role in human disease and establishing a direct disease link.

    Evidence Patient muscle biopsies, ectopic mutant PTRF expression in myoblasts, co-immunoprecipitation, rescue in patient fibroblasts with EM and AFM

    PMID:19726876 PMID:20300641

    Open questions at the time
    • Genotype–phenotype correlation across different PTRF mutations incomplete
    • Relative contributions of caveolar vs. nuclear PTRF functions to lipodystrophy phenotype unclear
  7. 2011 High

    CAVIN1 was found to participate in diverse cellular processes beyond caveola structure — membrane repair (by docking MG53 at injury sites), cellular senescence (by sequestering Mdm2 at caveolae to activate p53/p21), and dynamic nuclear-to-cytoplasmic translocation during senescence — revealing it as a signaling hub whose function depends on subcellular redistribution.

    Evidence RNAi, mutant PTRF expression, live-cell membrane repair imaging, co-IP with MG53; overexpression/shRNA with EM, luciferase reporter, subcellular fractionation for senescence pathway

    PMID:21343302 PMID:21445100 PMID:21705337

    Open questions at the time
    • How caveolar disassembly is sensed and triggers CAVIN1 release unknown
    • Direct mechanism of Mdm2 sequestration not structurally characterized
    • MG53–CAVIN1 interaction domain not mapped
  8. 2014 High

    The N-terminal leucine-zipper motif was identified as essential and sufficient for caveolae targeting, counteracting a central NLS, explaining the binary nuclear-vs-caveolar distribution; separately, CAVIN1's nuclear function in rRNA transcription was shown to be physiologically relevant in mature adipocytes responding to metabolic stress, providing a caveolae-independent explanation for lipodystrophy.

    Evidence Deletion mutant analysis with live-cell imaging and migration rescue; rDNA transcription assays in adipocytes with PTM mapping in PTRF-deficient mice

    PMID:25514038 PMID:27528195

    Open questions at the time
    • Signals that regulate the leucine-zipper/NLS competition in vivo not identified
    • Which PTMs specifically control rDNA transcription function remain to be mapped to individual sites
  9. 2016 High

    The structural basis of the CAVIN1 coat was resolved: purified CAVIN1 forms 60S complexes that assemble into flexible polyhedral lattices on membranes; two coiled-coil domains mediate distinct oligomerization and membrane-binding steps, and caveolin 8S oligomers occupy the faces of the polyhedra.

    Evidence Electron cryotomography and in vitro reconstitution on liposomes with coiled-coil domain mutagenesis

    PMID:27834731

    Open questions at the time
    • Atomic-resolution structure of the coat not available
    • How the coat accommodates different caveolar curvatures not explained
    • Stoichiometry of cavin1/cavin2/cavin3 subcomplexes in the coat unknown
  10. 2018 High

    CAVIN1 was shown to anchor SOCS3 at caveolae; the CAVIN1–SOCS3 interaction is essential for cAMP-induced inhibition of IL-6 signaling, establishing CAVIN1 as a platform for cytokine-signaling regulation at the plasma membrane.

    Evidence Reciprocal biochemical interaction, SOCS3 KO cells, confocal imaging, cytokine signaling assays in endothelial cells

    PMID:29330478

    Open questions at the time
    • Whether CAVIN1 recruits other SOCS family members unknown
    • Structural basis of the SOCS3–CAVIN1 interface not determined
  11. 2022 High

    The membrane-insertion mechanism was resolved at the biophysical level: PI(4,5)P2-dependent adsorption of the trimeric HR1 domain is followed by partial helix separation and insertion, with flanking disordered regions enhancing kinetics and co-assembly with caveolin-1, providing a detailed model of how CAVIN1 senses membrane composition.

    Evidence Model membrane biophysics, liposome binding assays, computational modeling, mutagenesis validated in live cells

    PMID:35696574

    Open questions at the time
    • How PI(4,5)P2 levels dynamically regulate caveola assembly/disassembly in vivo not shown
    • Whether other phosphoinositides modulate insertion unknown
  12. 2022 High

    A major signaling output of caveolar disassembly was identified: released cytoplasmic CAVIN1 directly binds NRF2 and promotes its degradation, maintaining cellular sensitivity to ferroptosis; this established a caveolae-to-oxidative-stress response signaling axis.

    Evidence Quantitative proteomics in CAVIN1 KO cells, reciprocal co-IP of CAVIN1–NRF2, live-cell caveolae imaging, zebrafish wound model

    PMID:36858041

    Open questions at the time
    • Whether CAVIN1 promotes NRF2 degradation via KEAP1-dependent or -independent ubiquitination unknown
    • Relative contribution of this pathway versus caveolar mechanoprotection to tissue homeostasis not quantified
  13. 2024 High

    CAVIN1 was placed in two new physiological contexts: it controls hERG potassium channel membrane dynamics in cardiomyocytes (affecting drug-induced QT prolongation), and it competes with BMPR2 for caveolin-1's scaffolding domain to modulate BMP/Smad signaling and pulmonary hypertension, extending the competition model for caveolin-1 interactions.

    Evidence iPS-CM electrophysiology with reciprocal gain/loss-of-function for hERG; co-IP domain mapping, hypoxia experiments in PAECs, and in vivo epistasis in pulmonary hypertension model for BMPR2

    PMID:38182755 PMID:38682330

    Open questions at the time
    • Whether CAVIN1-dependent hERG redistribution occurs via caveolar endocytosis or cytoskeletal sequestration is unresolved
    • How hypoxia increases CAVIN1–CAV1 interaction mechanistically is unknown
    • Therapeutic targetability of the CAVIN1–CAV1 competition not tested

Open questions

Synthesis pass · forward-looking unresolved questions
  • Major open questions remain: the atomic-resolution structure of the CAVIN1 coat and its dynamic remodeling under force; the precise signals and kinases that switch CAVIN1 between caveolar, cytosolic, and nuclear pools; whether CAVIN1's diverse cytosolic signaling partners (NRF2, paxillin, MG53, SOCS3) compete or are spatiotemporally segregated; and how caveolar versus nuclear CAVIN1 functions differentially contribute to human lipodystrophy and cardiometabolic disease.
  • No atomic-resolution structure of CAVIN1 coat or its individual domains
  • Kinase(s) regulating nuclear–caveolar shuttling not identified
  • Relative pathogenic contributions of caveolar vs. rRNA transcription defects in CAVIN1-linked lipodystrophy unknown

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0005198 structural molecule activity 4 GO:0060090 molecular adaptor activity 4 GO:0098772 molecular function regulator activity 4 GO:0003723 RNA binding 3 GO:0008289 lipid binding 3
Localization
GO:0005634 nucleus 5 GO:0005886 plasma membrane 5 GO:0005829 cytosol 2 GO:0031410 cytoplasmic vesicle 2
Pathway
R-HSA-162582 Signal Transduction 4 R-HSA-1852241 Organelle biogenesis and maintenance 4 R-HSA-74160 Gene expression (Transcription) 4 R-HSA-8953854 Metabolism of RNA 4 R-HSA-5357801 Programmed Cell Death 2 R-HSA-8953897 Cellular responses to stimuli 2 R-HSA-9612973 Autophagy 1
Partners
BMPR2CAV1CAV2CAV3NFE2L2PXNSOCS3TRIM72
Complex memberships
Caveolar coat complex (cavin1/cavin2/cavin3 with caveolin oligomers)

Evidence

Reading pass · 34 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
1998 PTRF (Cavin1) was cloned and shown to dissociate paused RNA Polymerase I ternary transcription complexes in vitro by releasing both nascent pre-rRNA transcripts and Pol I from the template; it interacts with TTF-I, Pol I, and the 3' end of pre-rRNA, with 3'-terminal uridylates essential for binding and release activity. In vitro transcription release assay with recombinant PTRF, protein–protein interaction studies, RNA-binding assay with 3'-end mutants The EMBO journal High 9582279
1999 PTRF interacts with the largest subunit of RNA Polymerase I and promotes dissociation of paused ternary transcription complexes through conserved interactions with Pol I and the termination factors TTF-I/Reb1p, but cannot release Pol I stalled by a non-termination factor (lac repressor), establishing specificity for termination-factor-dependent pausing. In vitro transcription termination assay using immobilized tailed templates from yeast and mouse; protein–protein interaction studies Molecular & general genetics High 10589839
2001 PTRF-mediated transcript release facilitates reinitiation of RNA Polymerase I transcription, thereby augmenting ribosomal RNA synthesis; PTRF is phosphorylated at multiple sites and fractionates into transcriptionally active and inactive forms, suggesting phosphorylation regulates its activity. Multiple-round and single-round in vitro transcription assays; reconstituted PTRF-free transcription system; phosphorylation analysis Nucleic acids research High 11139612
2004 PTRF is a major protein at the cytosolic surface of caveolae in human adipocytes, is phosphorylated at Ser-36, Ser-40, Ser-365, and Ser-366, and is subject to calpain-mediated cleavage at two sites within PEST domains, producing multiple truncated forms; co-localization with caveolin confirmed by immunofluorescence. Vectorial proteomics (differential proteolysis + MS on sealed caveolar vesicles), nanospray-quadrupole-TOF MS, immunofluorescence confocal microscopy The Biochemical journal High 15242332
2008 PTRF/Cavin1 is required for caveola formation and for sequestration of caveolin into immobile caveolae at the plasma membrane; without PTRF, caveolin resides on flat plasma membrane with increased lateral mobility and undergoes accelerated lysosomal degradation; expression of PTRF in caveolae-deficient PC3 cells is sufficient to induce caveola formation. Comparative proteomics, siRNA knockdown, ectopic expression in PC3 cells, zebrafish knockdown, FRAP, electron microscopy, live imaging Cell High 18191225
2008 Global deletion of Cavin1 in mice abolishes morphologically detectable caveolae in all cell types and markedly reduces protein expression of all three caveolin isoforms (while caveolin mRNA remains normal or elevated), demonstrating Cavin1 is essential for caveolae formation and post-translational stabilization of caveolins. Targeted gene disruption in mice, electron microscopy, immunoblotting, qRT-PCR Cell metabolism High 18840361
2009 Human PTRF mutations cause secondary deficiency and mislocalization of all three caveolin family members; disease-associated mutations cause PTRF mislocalization and disrupt its physical interaction with caveolins, confirming PTRF is required for caveolae formation and proper caveolin localization in human cells. Patient muscle biopsy analysis, ectopic expression of mutant PTRF constructs in myoblasts, co-immunoprecipitation, immunofluorescence The Journal of clinical investigation High 19726876
2010 In patient fibroblasts lacking PTRF, caveolin-1 fails to localize to the cell surface and caveolae are reduced to <3%; transfection of full-length PTRF re-establishes caveolae, confirming the essential and sufficient role of PTRF in caveola biogenesis. Patient fibroblast analysis, electron microscopy, Atomic Force Microscopy, transfection rescue PLoS genetics High 20300641
2010 PTRF/Cavin1 expression in PC3 prostate cancer cells reduces cell migration via decreased MMP9 production, and this effect is independent of caveola formation. Ectopic expression of PTRF in PC3 cells, cell migration assays, MMP9 ELISA/zymography European journal of cell biology Medium 20732728
2010 PTRF/Cavin1 interacts with the BFCOL1 zinc-finger transcription factor and enhances its binding to the mouse proalpha2(I) collagen proximal promoter in vitro, while suppressing promoter activity in transient transfection assays, indicating a role for PTRF in RNA Pol II transcription regulation. Yeast two-hybrid screening, in vitro EMSA, transient transfection reporter assay The Biochemical journal Medium 10727401
2011 PTRF acts as a docking protein for MG53 at plasma membrane injury sites, potentially by binding exposed membrane cholesterol; cells lacking PTRF show defective MG53 trafficking to injury sites, and a disease-associated PTRF mutation causes aberrant nuclear localization of PTRF and disrupts MG53-mediated membrane resealing; overexpression of PTRF rescues membrane repair defects in dystrophic muscle. RNAi knockdown, ectopic expression with mutant PTRF, live imaging of membrane repair, co-immunoprecipitation, fluorescence microscopy The Journal of biological chemistry High 21343302
2011 PTRF/Cavin1 expression is increased in senescent fibroblasts; PTRF overexpression induces cellular senescence via sequestration of Mdm2 into caveolar membranes away from p53, activating the p53/p21 pathway; a caveola-membrane-targeting-deficient PTRF mutant fails to activate p53 or senescence, and PTRF translocates from nucleus to cytosol/plasma membrane during senescence. Overexpression and shRNA knockdown, immunofluorescence, electron microscopy, luciferase reporter assay, subcellular fractionation, mutant PTRF expression The Journal of biological chemistry High 21705337
2011 PTRF/Cavin1 localizes to nuclei of young/quiescent fibroblasts and translocates to cytosol and plasma membrane during cellular senescence; the role of PTRF in senescence is dependent on its targeting to caveolae and interaction with caveolin-1, regulated by PTRF phosphorylation. Immunofluorescence, electron microscopy, overexpression/knockdown, phosphorylation analysis Cell research Medium 21445100
2011 PTRF expression modulates cholesterol distribution and impairs recruitment of actin cytoskeletal proteins to detergent-resistant membranes, leading to reduced prostasome secretion and decreased secretion of a subset of proteins including proteases, cytokines, and growth regulatory proteins. SILAC quantitative proteomics, subcellular fractionation, detergent-resistant membrane isolation, cholesterol modulation Molecular & cellular proteomics Medium 22030351
2012 PTRF/Cavin1 co-regulates cell polarization and migration with caveolin-1; PTRF modulates subcellular localization of Rac1, caveolin-1, and PKCα caveola recruitment in migrating cells; PTRF quantitatively reduces cell migration and induces mesenchymal-to-epithelial reversion, with caveola-independent functions identified. Fluorescence imaging, quantitative proteomics, cell migration assays, selective manipulation of PTRF and caveolin-1 expression in multiple cell systems PloS one Medium 22912783
2013 PTRF/Cavin1 neutralizes non-caveolar caveolin-1 microdomains in prostate cancer; cavin-1 co-expression reverses the oncogenic effects of caveolin-1 in caveolin-1-positive cells; absence of cavin-1 in advanced prostate cancer allows caveolin-1 to reside outside caveolae in tumor-promoting microdomains; cavin-1 reduces IL-6 microenvironmental function. Tissue microarray, ectopic expression in PC3/LNCaP/22Rv1 cells, anchorage-independent growth assays, orthotopic xenograft mouse model Oncogene Medium 23934189
2014 PTRF/Cavin1 promotes efficient rRNA transcription in response to metabolic challenges in mature adipocytes; multiple post-translational modifications of PTRF provide mechanistic bases for its regulation of rDNA transcription; this caveolae-independent nuclear function explains the lipodystrophy phenotype in PTRF-deficient mice and humans. rDNA transcription assays in mature adipocytes, analysis in PTRF-deficient mice, post-translational modification mapping eLife High 27528195
2014 SOCS3 localizes to the plasma membrane through interaction with cavin-1; deletion of SOCS3 reduces cavin-1 and caveolin-1 protein expression and reduces caveola abundance in endothelial cells; the cavin-1/SOCS3 interaction is essential for SOCS3-dependent inhibition of IL-6 signaling by cyclic AMP. Biochemical interaction studies, confocal imaging, SOCS3 knockout cells, cytokine signaling assays Nature communications High 29330478
2015 Cavin3 is targeted to caveolae by cavin1 where it interacts with the scaffolding domain of caveolin1 to promote caveolae dynamics; the N-terminal region of cavin3 binds a trimer of the cavin1 N-terminus in competition with cavin2, demonstrating distinct subcomplexes; loss of cavin3 increases stable caveolae and decreases transiently membrane-associated caveolae. Co-immunoprecipitation, TIRF/live-cell imaging, N-terminal binding competition assays, cavin3 KD cells Journal of cell science High 25588833
2016 Purified Cavin1 forms 60S complexes that adopt a flexible, net-like protein mesh forming polyhedral lattices on phosphatidylserine-containing vesicles; the two coiled-coil domains mediate distinct assembly steps; positive residues around the C-terminal coiled-coil domain are required for membrane binding; caveolin 8S oligomers form disc-shaped arrangements consistent with occupying the faces of caveolar polyhedra. Electron cryotomography, in vitro reconstitution on liposomes, coiled-coil domain mutagenesis, purified protein structural analysis PNAS High 27834731
2016 ROR1 functions as a scaffold for cavin-1 and caveolin-1 at the plasma membrane in a kinase-independent manner, facilitating their interaction and preventing lysosomal degradation of caveolin-1, thereby sustaining caveolae structures and pro-survival AKT signaling. Co-immunoprecipitation, immunofluorescence, ROR1 mutant expression, lysosomal inhibitor experiments Nature communications High 26725982
2014 The N-terminal leucine-zipper motif of PTRF/Cavin1 is essential and sufficient for its caveolae association at the plasma membrane, counteracting its nuclear localization sequence (AA 235-251); deletion of this motif causes exclusive nuclear localization; caveolae-associated PTRF is required for its role in cell migration. Deletion mutant expression, live-cell fluorescence imaging, fusion protein nuclear export assay, MEF migration assay with PTRF mutant rescue Biochemical and biophysical research communications Medium 25514038
2019 High glucose promotes LDL transcytosis across endothelial cells by inhibiting the AMPK-mTOR-PIK3C3 pathway, which suppresses CAV1-CAVIN1-LC3B-mediated autophagic degradation of CAV1, leading to CAV1 accumulation, more caveolae formation, and increased LDL transcytosis. siRNA knockdown, AMPK/mTOR/PIK3C3 pathway inhibition, LDL transcytosis assay, autophagy flux analysis, immunoblotting Autophagy Medium 31448673
2019 Cavin-1 is acutely translocated to focal complex compartments upon insulin stimulation, where it regulates focal complex formation through interaction with paxillin; loss of cavin-1 impairs focal complex remodeling and focal adhesion formation and causes a mechanical stress response with activation of proinflammatory and senescence/apoptosis pathways. Cavin-1 knockout mice, subcellular fractionation, immunoblotting, co-immunoprecipitation with paxillin, insulin stimulation assays The Journal of biological chemistry Medium 31126986
2021 Caveolin-1 and cavin1 individually sort distinct plasma membrane lipids; intact caveolar structures composed of both proteins generate a unique lipid nano-environment with selectivity for specific lipid headgroups and acyl chains. Quantitative nanoscale lipid mapping (STED-based), molecular dynamic simulations, genome-edited cells lacking CAV1 or cavin1 The Journal of cell biology High 33496726
2022 PTRF/Cavin1 acts as a novel RNA-binding protein that stabilizes lncRNA NEAT1, which in turn suppresses UBXN1 and activates NF-κB, driving PD-L1 transcription and promoting immune evasion in glioblastoma. RIP-Seq, RIP assay, ChIP, co-immunoprecipitation, qRT-PCR, PD-L1 reporter assay Frontiers in immunology Medium 35069587
2022 Membrane insertion of Cavin1 occurs via PI(4,5)P2-dependent adsorption of the trimeric helical region 1 (HR1) followed by partial separation and membrane insertion of individual helices; insertion kinetics are enhanced by flanking negatively charged disordered regions important for co-assembly with Caveolin1 in living cells. Model membrane biophysics, liposome binding assays, computational modeling, mutagenesis, live-cell imaging of Cavin1-Caveolin1 co-assembly PNAS High 35696574
2022 Oxidative stress triggers lipid peroxidation and caveolar disassembly, releasing CAVIN1 from caveolae; released cytoplasmic CAVIN1 directly interacts with NRF2 and facilitates its degradation, thereby maintaining cellular susceptibility to oxidative-stress-induced cell death (ferroptosis); CAVIN1-null cells show impaired NRF2 negative regulation and resistance to lipid-peroxidation-induced ferroptosis. Quantitative whole-cell proteomics of genome-edited CAVIN1-null cells, co-immunoprecipitation of CAVIN1–NRF2, live-cell caveolae imaging, zebrafish wound model Developmental cell High 36858041
2022 Caveola deformation (by osmotic stress) causes relocalization of cavin-1 to the nucleus, altering global transcription and translation; cavin-1 levels affect cytosolic RNA levels and the ability to form stress granules and p-bodies; Cav1-Gαq contact changes upon stimulation also trigger cavin-1 relocalization. Osmotic stress experiments, cavin-1 KO cell line, live-cell imaging, stress granule/p-body quantification, RNA level analysis The Journal of biological chemistry Medium 35513070
2022 UBE2O ubiquitinates PTRF/CAVIN1 directly and inhibits its effects on exosome secretion by decreasing caveolae formation; SDPR/CAVIN2 interacts with both UBE2O and PTRF and promotes PTRF expression in exosomes; UBE2O decreases exosome secretion and downregulates exosomal PTRF secretion. Exogenous and endogenous co-immunoprecipitation, ubiquitination assays, ultracentrifugation exosome isolation, nanoparticle tracking analysis, electron microscopy Cell communication and signaling Medium 36443833
2022 PTRF/Cavin1 stabilizes cPLA2 by decreasing its proteasome-mediated degradation, resulting in increased cPLA2 activity and remodeled phospholipid composition in glioblastoma cells; this promotes tumor proliferation and suppresses CD8+ tumor-infiltrating lymphocytes. Co-immunoprecipitation, ubiquitination/proteasome inhibitor assays, nontargeted metabolomics, lipidomics, in vivo xenograft and intracranial tumor models Neuro-oncology Medium 33140095
2024 CAVIN1 controls hERG potassium channel dynamics at the cardiac plasma membrane; elevated CAVIN1 promotes sotalol-induced translocation of hERG from the plasma membrane to cytoskeleton-associated fractions, reducing IKr and prolonging repolarization; CAVIN1 knockdown abrogates this translocation and reduces susceptibility to drug-induced long QT. iPS-CM electrophysiology, siRNA knockdown, adenoviral CAVIN1 overexpression, cellular hERG distribution imaging, sotalol/E4031/vandetanib/clarithromycin treatments Circulation High 38682330
2024 Cavin-1 competes with BMPR2 for binding to the scaffolding domain of Caveolin-1; hypoxia enhances the Cavin-1/CAV1 interaction while attenuating the CAV1/BMPR2 interaction and BMPR2 membrane localization; Cavin-1 reduces BMPR2 membrane localization and Smad signal transduction in pulmonary artery endothelial cells; Cavin-1 knockdown is resistant to CAV1-induced pulmonary hypertension in vivo. Co-immunoprecipitation of CAV1/Cavin-1/BMPR2 complexes, domain mapping, hypoxia experiments in PAECs, Cavin-1 knockdown in vivo pulmonary hypertension model Communications biology High 38182755
2020 Cavin-1 deficiency inhibits the RhoA-ROCK2-LIMK-Cofilin signaling pathway and suppresses cytoskeletal dynamics in liver sinusoidal endothelial cells, causing reduction of fenestrae and impaired liver permeability leading to defective hepatic glycogen metabolism and neonatal hypoglycemia; F-actin depolymerization with latrunculin A rescues fenestration defects. Cavin1 KO mice (C57BL/6J), electron microscopy, signaling pathway analysis, latrunculin A rescue experiment Advanced science Medium 33042738

Source papers

Stage 0 corpus · 100 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2008 PTRF-Cavin, a conserved cytoplasmic protein required for caveola formation and function. Cell 590 18191225
2009 Human PTRF mutations cause secondary deficiency of caveolins resulting in muscular dystrophy with generalized lipodystrophy. The Journal of clinical investigation 302 19726876
2008 Deletion of Cavin/PTRF causes global loss of caveolae, dyslipidemia, and glucose intolerance. Cell metabolism 292 18840361
2010 Fatal cardiac arrhythmia and long-QT syndrome in a new form of congenital generalized lipodystrophy with muscle rippling (CGL4) due to PTRF-CAVIN mutations. PLoS genetics 180 20300641
1998 Cloning and functional characterization of PTRF, a novel protein which induces dissociation of paused ternary transcription complexes. The EMBO journal 128 9582279
2004 Vectorial proteomics reveal targeting, phosphorylation and specific fragmentation of polymerase I and transcript release factor (PTRF) at the surface of caveolae in human adipocytes. The Biochemical journal 124 15242332
2018 The role of PTRF/Cavin1 as a biomarker in both glioma and serum exosomes. Theranostics 109 29556340
2010 Congenital generalized lipodystrophy, type 4 (CGL4) associated with myopathy due to novel PTRF mutations. American journal of medical genetics. Part A 102 20684003
2011 Polymerase transcriptase release factor (PTRF) anchors MG53 protein to cell injury site for initiation of membrane repair. The Journal of biological chemistry 91 21343302
2014 Cavin-1/PTRF alters prostate cancer cell-derived extracellular vesicle content and internalization to attenuate extracellular vesicle-mediated osteoclastogenesis and osteoblast proliferation. Journal of extracellular vesicles 85 25018864
2022 Neuronal STAT3/HIF-1α/PTRF axis-mediated bioenergetic disturbance exacerbates cerebral ischemia-reperfusion injury via PLA2G4A. Theranostics 82 35547748
2016 ROR1 sustains caveolae and survival signalling as a scaffold of cavin-1 and caveolin-1. Nature communications 75 26725982
2016 Model for the architecture of caveolae based on a flexible, net-like assembly of Cavin1 and Caveolin discs. Proceedings of the National Academy of Sciences of the United States of America 75 27834731
2019 CAV1-CAVIN1-LC3B-mediated autophagy regulates high glucose-stimulated LDL transcytosis. Autophagy 71 31448673
2013 PTRF/cavin-1 neutralizes non-caveolar caveolin-1 microdomains in prostate cancer. Oncogene 65 23934189
2012 PTRF/cavin-1 and MIF proteins are identified as non-small cell lung cancer biomarkers by label-free proteomics. PloS one 65 22461895
2010 PTRF-cavin-1 expression decreases the migration of PC3 prostate cancer cells: role of matrix metalloprotease 9. European journal of cell biology 63 20732728
2011 Expression of PTRF in PC-3 Cells modulates cholesterol dynamics and the actin cytoskeleton impacting secretion pathways. Molecular & cellular proteomics : MCP 59 22030351
2011 Regulation of cellular senescence by the essential caveolar component PTRF/Cavin-1. Cell research 58 21445100
1999 Mechanism of transcription termination: PTRF interacts with the largest subunit of RNA polymerase I and dissociates paused transcription complexes from yeast and mouse. Molecular & general genetics : MGG 56 10589839
2014 Pleiotropic effects of cavin-1 deficiency on lipid metabolism. The Journal of biological chemistry 55 24509860
2021 PTRF/cavin-1 remodels phospholipid metabolism to promote tumor proliferation and suppress immune responses in glioblastoma by stabilizing cPLA2. Neuro-oncology 53 33140095
2013 Caveolin-1/PTRF upregulation constitutes a mechanism for mediating p53-induced cellular senescence: implications for evidence-based therapy of delayed wound healing in diabetes. American journal of physiology. Endocrinology and metabolism 52 23941874
2012 Co-regulation of cell polarization and migration by caveolar proteins PTRF/Cavin-1 and caveolin-1. PloS one 52 22912783
2010 Changes in caveolae, caveolin, and polymerase 1 and transcript release factor (PTRF) expression in prostate cancer progression. The Prostate 52 20564315
2010 A Japanese child with asymptomatic elevation of serum creatine kinase shows PTRF-CAVIN mutation matching with congenital generalized lipodystrophy type 4. Molecular genetics and metabolism 51 20638880
2021 Caveolin-1 and cavin1 act synergistically to generate a unique lipid environment in caveolae. The Journal of cell biology 50 33496726
2013 Caveola-forming proteins caveolin-1 and PTRF in prostate cancer. Nature reviews. Urology 49 23938946
2000 PTRF (polymerase I and transcript-release factor) is tissue-specific and interacts with the BFCOL1 (binding factor of a type-I collagen promoter) zinc-finger transcription factor which binds to the two mouse type-I collagen gene promoters. The Biochemical journal 49 10727401
2013 PTRF/cavin-1 is essential for multidrug resistance in cancer cells. Journal of proteome research 47 23214712
2001 The transcript release factor PTRF augments ribosomal gene transcription by facilitating reinitiation of RNA polymerase I. Nucleic acids research 46 11139612
2015 Cavin3 interacts with cavin1 and caveolin1 to increase surface dynamics of caveolae. Journal of cell science 45 25588833
2016 PTRF/Cavin-1 promotes efficient ribosomal RNA transcription in response to metabolic challenges. eLife 44 27528195
2011 Polymerase I and transcript release factor (PTRF)/cavin-1 is a novel regulator of stress-induced premature senescence. The Journal of biological chemistry 43 21705337
2013 Novel PTRF mutation in a child with mild myopathy and very mild congenital lipodystrophy. BMC medical genetics 42 24024685
2010 IGF-IR internalizes with Caveolin-1 and PTRF/Cavin in HaCat cells. PloS one 40 21152401
2013 PTRF/Cavin-1 decreases prostate cancer angiogenesis and lymphangiogenesis. Oncotarget 39 24123650
2010 Quantitative proteomics of caveolin-1-regulated proteins: characterization of polymerase i and transcript release factor/CAVIN-1 IN endothelial cells. Molecular & cellular proteomics : MCP 38 20585024
2015 Cavin-1 and Caveolin-1 are both required to support cell proliferation, migration and anchorage-independent cell growth in rhabdomyosarcoma. Laboratory investigation; a journal of technical methods and pathology 33 25822667
2022 PTRF/Cavin-1 enhances chemo-resistance and promotes temozolomide efflux through extracellular vesicles in glioblastoma. Theranostics 32 35673568
2022 PTRF/Cavin-1 as a Novel RNA-Binding Protein Expedites the NF-κB/PD-L1 Axis by Stabilizing lncRNA NEAT1, Contributing to Tumorigenesis and Immune Evasion in Glioblastoma. Frontiers in immunology 31 35069587
2015 Novel nonsense mutation in the PTRF gene underlies congenital generalized lipodystrophy in a consanguineous Saudi family. European journal of medical genetics 31 25721873
2020 PTRF/CAVIN1, regulated by SHC1 through the EGFR pathway, is found in urine exosomes as a potential biomarker of ccRCC. Carcinogenesis 30 31605605
2016 PTRF/Cavin-1 Deficiency Causes Cardiac Dysfunction Accompanied by Cardiomyocyte Hypertrophy and Cardiac Fibrosis. PloS one 29 27612189
2014 Hypoxia inhibits Cavin-1 and Cavin-2 expression and down-regulates caveolae in adipocytes. Endocrinology 29 25521582
2015 Galectin-3 Overrides PTRF/Cavin-1 Reduction of PC3 Prostate Cancer Cell Migration. PloS one 28 25942420
2010 Caveolin-1 induces formation of membrane tubules that sense actomyosin tension and are inhibited by polymerase I and transcript release factor/cavin-1. Molecular biology of the cell 28 20427576
2023 Caveolae sense oxidative stress through membrane lipid peroxidation and cytosolic release of CAVIN1 to regulate NRF2. Developmental cell 27 36858041
2018 Interaction of suppressor of cytokine signalling 3 with cavin-1 links SOCS3 function and cavin-1 stability. Nature communications 27 29330478
2017 MiR-217 promotes cutaneous squamous cell carcinoma progression by targeting PTRF. American journal of translational research 26 28337292
2014 Arterial dysfunction but maintained systemic blood pressure in cavin-1-deficient mice. PloS one 26 24658465
2013 Elevated pulmonary arterial pressure and altered expression of Ddah1 and Arg1 in mice lacking cavin-1/PTRF. Physiological reports 26 24303100
2008 PTRF triggers a cave in. Cell 26 18191216
2016 DNA methylation profiling identifies PTRF/Cavin-1 as a novel tumor suppressor in Ewing sarcoma when co-expressed with caveolin-1. Cancer letters 25 27894957
2014 Polymerase I and transcript release factor (PTRF) regulates adipocyte differentiation and determines adipose tissue expandability. FASEB journal : official publication of the Federation of American Societies for Experimental Biology 25 24812087
2013 Cavin1; a regulator of lung function and macrophage phenotype. PloS one 24 23634221
2020 Lessons from cavin-1 deficiency. Biochemical Society transactions 23 31922193
2014 Cavin-1: caveolae-dependent signalling and cardiovascular disease. Biochemical Society transactions 23 24646232
2012 Impaired contractility and detrusor hypertrophy in cavin-1-deficient mice. European journal of pharmacology 23 22643325
2017 Cavin-1 regulates caveolae-mediated LDL transcytosis: crosstalk in an AMPK/eNOS/ NF-κB/Sp1 loop. Oncotarget 22 29262615
2023 Non-alcoholic fatty liver disease combined with rheumatoid arthritis exacerbates liver fibrosis by stimulating co-localization of PTRF and TLR4 in rats. Frontiers in pharmacology 21 37346294
2017 MicroRNA-187 modulates epithelial-mesenchymal transition by targeting PTRF in non-small cell lung cancer. Oncology reports 21 28393200
2014 Emerging role of polymerase-1 and transcript release factor (PTRF/ Cavin-1) in health and disease. Cell and tissue research 21 25107607
2023 PTRF-IL33-ZBP1 signaling mediating macrophage necroptosis contributes to HDM-induced airway inflammation. Cell death & disease 20 37454215
2015 Caveolae, caveolin-1 and cavin-1: Emerging roles in pulmonary hypertension. World journal of respirology 20 28529892
2023 Neovascularization directed by CAVIN1/CCBE1/VEGFC confers TMZ-resistance in glioblastoma. Cancer letters 18 38092144
2019 Correlation of the invasive potential of glioblastoma and expression of caveola-forming proteins caveolin-1 and CAVIN1. Journal of neuro-oncology 18 30949900
2022 UBE2O ubiquitinates PTRF/CAVIN1 and inhibits the secretion of exosome-related PTRF/CAVIN1. Cell communication and signaling : CCS 17 36443833
2022 Membrane insertion mechanism of the caveola coat protein Cavin1. Proceedings of the National Academy of Sciences of the United States of America 16 35696574
2019 Postmortem Findings in a Young Man With Congenital Generalized Lipodystrophy, Type 4 Due to CAVIN1 Mutations. The Journal of clinical endocrinology and metabolism 16 30476128
2017 Cavin-1 deficiency modifies myocardial and coronary function, stretch responses and ischaemic tolerance: roles of NOS over-activity. Basic research in cardiology 16 28343262
2016 Knockdown of PTRF ameliorates adipocyte differentiation and functionality of human mesenchymal stem cells. American journal of physiology. Cell physiology 16 27856429
2023 A new mutation in the CAVIN1/PTRF gene in two siblings with congenital generalized lipodystrophy type 4: case reports and review of the literature. Frontiers in endocrinology 15 37501786
2020 Homotrimer cavin1 interacts with caveolin1 to facilitate tumor growth and activate microglia through extracellular vesicles in glioma. Theranostics 15 32550897
2017 PTRF suppresses the progression of colorectal cancers. Oncotarget 15 27203393
2017 Muscular dystrophy in PTFR/cavin-1 null mice. JCI insight 15 28289716
2016 Caveolin-1, Caveolin-2 and Cavin-1 are strong predictors of adipogenic differentiation in human tumors and cell lines of liposarcoma. European journal of cell biology 15 27168348
2016 Maladaptative Autophagy Impairs Adipose Function in Congenital Generalized Lipodystrophy due to Cavin-1 Deficiency. The Journal of clinical endocrinology and metabolism 14 27144934
2023 Serum amyloid A and interleukin -1β facilitate LDL transcytosis across endothelial cells and atherosclerosis via NF-κB/caveolin-1/cavin-1 pathway. Atherosclerosis 13 36935311
2014 Increased polymerase I and transcript release factor (Cavin-1) expression attenuates platelet-derived growth factor receptor signalling in senescent human fibroblasts. Clinical and experimental pharmacology & physiology 12 24471649
2020 A role for caveola-forming proteins caveolin-1 and CAVIN1 in the pro-invasive response of glioblastoma to osmotic and hydrostatic pressure. Journal of cellular and molecular medicine 11 32065471
2019 Metreleptin treatment for congenital generalized lipodystrophy type 4 (CGL4): a case report. Clinical pediatric endocrinology : case reports and clinical investigations : official journal of the Japanese Society for Pediatric Endocrinology 11 30745727
2014 The N-terminal leucine-zipper motif in PTRF/cavin-1 is essential and sufficient for its caveolae-association. Biochemical and biophysical research communications 11 25514038
2011 A study of FHL1, BAG3, MATR3, PTRF and TCAP in Australian muscular dystrophy patients. Neuromuscular disorders : NMD 11 21683594
2024 EPIC-1042 as a potent PTRF/Cavin1-caveolin-1 interaction inhibitor to induce PARP1 autophagic degradation and suppress temozolomide efflux for glioblastoma. Neuro-oncology 10 37651725
2017 Downregulation of Cavin-1 Expression via Increasing Caveolin-1 Degradation Prompts the Proliferation and Migration of Vascular Smooth Muscle Cells in Balloon Injury-Induced Neointimal Hyperplasia. Journal of the American Heart Association 10 28751541
2024 The Cavin-1/Caveolin-1 interaction attenuates BMP/Smad signaling in pulmonary hypertension by interfering with BMPR2/Caveolin-1 binding. Communications biology 9 38182755
2022 Cavin-1 promotes M2 macrophages/microglia polarization via SOCS3. Inflammation research : official journal of the European Histamine Research Society ... [et al.] 9 35275225
2021 Suppression of PTRF Alleviates Post-Infectious Irritable Bowel Syndrome via Downregulation of the TLR4 Pathway in Rats. Frontiers in pharmacology 9 34690766
2019 Cavin-1/PTRF mediates insulin-dependent focal adhesion remodeling and ameliorates high-fat diet-induced inflammatory responses in mice. The Journal of biological chemistry 9 31126986
2020 Cavin1 Deficiency Causes Disorder of Hepatic Glycogen Metabolism and Neonatal Death by Impacting Fenestrations in Liver Sinusoidal Endothelial Cells. Advanced science (Weinheim, Baden-Wurttemberg, Germany) 8 33042738
2019 PTRF independently predicts progression and survival in multiracial upper tract urothelial carcinoma following radical nephroureterectomy. Urologic oncology 8 31862213
2023 Defected lipid rafts suppress cavin1-dependent IFN-α signaling endosome in paroxysmal nocturnal hemoglobinuria. International immunopharmacology 7 36608443
2023 Cavin1 activates the Wnt/β-catenin pathway to influence the proliferation and migration of hepatocellular carcinoma. Annals of hepatology 7 37774837
2021 Deficiency of cold-inducible RNA-binding protein exacerbated monocrotaline-induced pulmonary artery hypertension through Caveolin1 and CAVIN1. Journal of cellular and molecular medicine 7 33755319
2020 Unusual clinical features associated with congenital generalized lipodystrophy type 4 in a patient with a novel E211X CAVIN1 gene variant. Clinical diabetes and endocrinology 7 32467771
2022 Deformation of caveolae impacts global transcription and translation processes through relocalization of cavin-1. The Journal of biological chemistry 6 35513070
2018 Ptrf transgenic mice exhibit obesity and fatty liver. Clinical and experimental pharmacology & physiology 5 29381831
2024 CAVIN1-Mediated hERG Dynamics: A Novel Mechanism Underlying the Interindividual Variability in Drug-Induced Long QT. Circulation 4 38682330
2022 Congenital generalized lipodystrophy type 4 due to a novel PTRF/CAVIN1 pathogenic variant in a child: effects of metreleptin substitution. Journal of pediatric endocrinology & metabolism : JPEM 4 35405042