Affinage

ANKRD1

Ankyrin repeat domain-containing protein 1 · UniProt Q15327

Length
319 aa
Mass
36.3 kDa
Annotated
2026-06-09
52 papers in source corpus 28 papers cited in narrative 28 extracted findings
Cross-family judge vs UniProt: Affinage preferred faithfulness: 7/7 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

ANKRD1/CARP is a stress-inducible, dual-compartment protein that couples the mechanical state of the sarcomere to gene expression, with broader roles in tissue injury, fibroblast activation, and cell motility (PMID:19608031, PMID:25770146). In striated muscle it resides at the sarcomeric I-band through direct binding to the titin N2A domain and myopalladin, and to cardiac calsequestrin-2, with disease-associated mutations altering these interactions and CARP localization (PMID:19608031, PMID:15698842). ANKRD1 translocates to the nucleus where it acts as a context-dependent transcriptional coregulator: it represses ANF, MMP13/MMP10 (via the AP-1 site, opposing c-Jun binding), and androgen-receptor target genes, while co-activating p53 to induce TP53, BAX and CDKN1A and destabilize MDM2 (PMID:24515436, PMID:23811403, PMID:29179447). It relays hypertrophic signaling as part of an ANKRD1/ERK1/2/GATA4 complex that translocates to the nucleus upon adrenergic stimulation, with Ankrd1 required for phenylephrine-induced but not pressure-overload hypertrophy, and it feeds back on inflammatory signaling by binding the NF-κB p50 subunit to inhibit TNFα-induced transcription (PMID:25770146, PMID:26102030). ANKRD1 abundance is tightly controlled by 26S proteasome-mediated degradation through a PEST motif and additional degrons, while its mRNA is stabilized by the RNA-binding protein RBMS1 during senescence (PMID:19589340, PMID:22892129, PMID:38769646). Beyond muscle, ANKRD1 drives cancer-associated fibroblast activation under androgen-receptor negative control by promoting c-JUN/FOS (AP-1) association at effector gene loci, regulates cell spreading, migration and lamellipodia formation through talin-1 and the integrin/FAK pathway, and promotes ferroptosis by facilitating TRIM25-mediated K63-ubiquitination and degradation of ACSL3 (PMID:38310103, PMID:25452119, PMID:40362467, PMID:39285846). Compartment-specific studies indicate nuclear ANKRD1 exacerbates pathological cardiac remodeling whereas cytosolic ANKRD1 is cardioprotective, and blocking its nuclear import improves cardiac function (PMID:38475992).

Mechanistic history

Synthesis pass · year-by-year structured walk · 24 steps
  1. 2005 High

    Established that ANKRD1 has a direct structural partner in the cardiac calcium-handling apparatus, anchoring it in the heart beyond a purely nuclear role.

    Evidence Pull-down, blot-overlay, Co-IP and peptide mapping from heart extracts with immunohistochemistry

    PMID:15698842

    Open questions at the time
    • Functional consequence of the ANKRD1–CASQ2 interaction for calcium handling not defined
    • Whether binding is dynamic or constitutive unresolved
  2. 2008 Medium

    Linked ANKRD1 protein stability to its transcriptional repressor function, showing a disease mutation that stabilizes the protein and enhances repression of the ANF promoter.

    Evidence In vitro calpain degradation assay and reporter gene assay in HeLa cells with a TAPVR-associated mutation

    PMID:18273862

    Open questions at the time
    • Mechanism connecting stability to repression not resolved
    • Calpain role in vivo not tested
  3. 2009 High

    Defined ANKRD1 as a node in sarcomeric stretch sensing by mapping cardiomyopathy mutations onto titin/myopalladin and talin-1/FHL2 interactions and onto altered stretch-induced and repressor activity.

    Evidence Co-IP and localization in neonatal rat cardiomyocytes, yeast two-hybrid, stretch and reporter/hypertrophy assays with HCM and DCM mutants

    PMID:19525294 PMID:19608030 PMID:19608031

    Open questions at the time
    • Direct demonstration that mutant binding changes cause disease in vivo lacking at this stage
    • Whether stretch directly modulates ANKRD1 conformation untested
  4. 2009 Medium

    Identified the proteasome and a PEST motif as the principal control of ANKRD1 turnover, framing it as a rapidly degraded stress-inducible factor.

    Evidence Proteasome inhibitor treatment, PEST motif mutagenesis, and pulse-chase analysis

    PMID:19589340

    Open questions at the time
    • Responsible E3 ligase not identified
    • Other contributing degrons uncharacterized
  5. 2010 Medium

    Placed ANKRD1 in a reciprocal regulatory loop with p53, acting as a co-activator while being a p53 transcriptional target.

    Evidence Protein array, in vivo/in vitro Co-IP, and promoter reporter assay

    PMID:20599664

    Open questions at the time
    • Mechanism of p53 co-activation undefined
    • Physiological context of the loop not established
  6. 2012 Medium

    Demonstrated co-dependence of ANKRD1 and GATA4 for myofilament gene expression and sarcomere integrity, with GATA4 driving the ANKRD1 promoter.

    Evidence Reporter assay, siRNA knockdown, adenoviral overexpression and doxorubicin rescue in cardiomyocytes

    PMID:22532871

    Open questions at the time
    • Direct ANKRD1 occupancy of myofilament gene promoters not shown
    • Single-lab in vitro evidence
  7. 2012 Medium

    Showed cell-type-specific control of ANKRD1 half-life by the proteasome, explaining short-lived versus stable pools across cardiomyocytes and endothelium.

    Evidence Proteasome inhibition and pulse-chase half-life measurement in rat ventricular myocytes and endothelial cells

    PMID:22892129

    Open questions at the time
    • Molecular basis for cell-type differences in half-life unknown
    • Density-dependent degradation mechanism unresolved
  8. 2013 Medium

    Resolved that distinct HCM mutations act through different mechanisms—gain-of-function versus proteasome-driven instability and dominant-negative effects—directly tying degradation to contractile phenotype.

    Evidence AAV gene transfer into engineered heart tissue with contractile analysis and proteasome inhibition

    PMID:23572067

    Open questions at the time
    • Patient-level causality not established
    • How instability translates to relaxation defects mechanistically unclear
  9. 2013 Medium

    Extended ANKRD1's repressor role to androgen-receptor signaling in muscle, with testosterone downregulating Ankrd1 and ANKRD1 repressing AR target genes.

    Evidence Co-IP and ARE/MAFbx reporter assays with testosterone-regulated gene qPCR in myoblasts

    PMID:23811403

    Open questions at the time
    • Whether ANKRD1 binds AR target promoters directly not shown
    • In vivo relevance untested
  10. 2014 High

    Defined a transcriptional repression mechanism in which ANKRD1 antagonizes c-Jun at AP-1 sites to silence matrix metalloproteinases, validated in knockout fibroblasts.

    Evidence Yeast two-hybrid, Co-IP, EMSA, ChIP, promoter assays and Ankrd1-null mouse analysis

    PMID:24515436

    Open questions at the time
    • Role of the nucleolin interaction unclear
    • Direct DNA binding versus AP-1 sequestration not fully separated
  11. 2014 High

    Established ANKRD1 as required for fibroblast spreading, migration, collagen contraction and wound healing, demonstrating a non-muscle structural/motility function in vivo.

    Evidence Global Ankrd1 KO mouse with migration, 3D gel contraction, adenoviral rescue, and wound/ischemic flap models

    PMID:25452119

    Open questions at the time
    • Molecular effector linking ANKRD1 to actin organization not pinpointed here
    • Cell-autonomous versus systemic contribution not dissected
  12. 2015 High

    Identified the ANKRD1/ERK1/2/GATA4 signaling complex as the relay for adrenergic hypertrophy, with stimulus-specific requirement for Ankrd1.

    Evidence Co-IP, siRNA knockdown, adrenergic stimulation, and Ankrd1 KO mice with PE infusion versus TAC

    PMID:25770146

    Open questions at the time
    • How ANKRD1 selectively couples to PE but not pressure-overload signaling unknown
    • Direct contacts within the complex not mapped
  13. 2015 Medium

    Showed ANKRD1 provides feedback inhibition of inflammatory signaling by binding NF-κB p50 and occupying an NF-κB site in the ANKRD2 promoter.

    Evidence Co-IP, siRNA, NF-κB reporter and ChIP in C2C12 myoblasts

    PMID:26102030

    Open questions at the time
    • Structural basis of p50 binding undefined
    • In vivo significance of the feedback loop untested
  14. 2015 Medium

    Connected ANKRD1 to catecholamine biosynthesis, with ERK5 inducing it and ANKRD1 stabilizing tyrosine hydroxylase by reducing its ubiquitination.

    Evidence Microarray with ERK5/ERK1/2 inhibitors, siRNA, ubiquitination and catecholamine assays in PC12 cells

    PMID:26739108

    Open questions at the time
    • Mechanism by which ANKRD1 reduces TH ubiquitination unknown
    • Relevance to neuronal physiology in vivo untested
  15. 2017 Medium

    Positioned ANKRD1 in the Hippo-RASSF1A axis as a YAP1 target that suppresses cancer cell growth in a p53-dependent manner.

    Evidence Reporter/expression assays, Co-IP, and colony formation in cancer cells

    PMID:29179447

    Open questions at the time
    • Direct ANKRD1 regulation of MDM2 stability not mechanistically defined
    • Tumor-context specificity unclear
  16. 2019 High

    Showed gain of ANKRD1 in myocardium causes developmental and diastolic cardiac defects, reinforcing dose- and compartment-sensitive function and dynamic nucleo-sarcomeric localization.

    Evidence Myocardium-specific transgenic mice with histology, hemodynamics, myofibrillar assays and transcriptional profiling

    PMID:31688894

    Open questions at the time
    • Trigger for nuclear versus sarcomeric partitioning not defined
    • Link between titin gene changes and dysfunction not mechanistically closed
  17. 2023 Low

    Began to link ANKRD1 to ferroptosis through p53/SLC7A11/GPX4 in renal tubular cells.

    Evidence Lentiviral silencing/overexpression with Western blot of ferroptosis markers and Fe2+ assay in HK-2 cells

    PMID:36907445

    Open questions at the time
    • No direct epistasis experiment—pathway position inferred from marker changes only
    • Single-lab Western-blot readout
    • Direct ANKRD1 target in this axis not identified
  18. 2023 Medium

    Implicated ANKRD1 in osteogenic differentiation via CAV3 deubiquitination and Wnt/β-catenin activation.

    Evidence Lentiviral manipulation in BMSCs with ubiquitination assay and CAV3-knockdown epistasis

    PMID:36958710

    Open questions at the time
    • How ANKRD1 reduces CAV3 ubiquitination unknown
    • In vivo bone phenotype untested
  19. 2024 High

    Defined ANKRD1 as an AR-repressed mesenchymal coregulator driving cancer-associated fibroblast activation through AP-1 (c-JUN/FOS) cooperation.

    Evidence ChIP, AP-1 Co-IP, knockdown, AR manipulation and orthotopic skin cancer model

    PMID:38310103

    Open questions at the time
    • Whether ANKRD1 directly contacts AP-1 components mapped only by Co-IP
    • Generalizability beyond skin tumor context unestablished
  20. 2024 High

    Showed ANKRD1 promotes ferroptosis by enabling TRIM25-mediated K63-ubiquitination and degradation of ACSL3 in renal ischemia-reperfusion.

    Evidence IP-MS interactome, Co-IP, proximity ligation, ubiquitination assay and rAAV9 knockdown in vivo

    PMID:39285846

    Open questions at the time
    • How ANKRD1 facilitates TRIM25 activity mechanistically unclear
    • Relationship to the p53/SLC7A11 ferroptosis route not reconciled
  21. 2024 Medium

    Demonstrated opposing roles of nuclear versus cytosolic ANKRD1 in heart failure and identified AGO2-driven transcription and NLS-blocking peptides as therapeutic levers.

    Evidence Compartment-specific AAV9 overexpression, TAC model, reporter assays and pharmacological intervention (ivermectin, ANPep)

    PMID:38475992

    Open questions at the time
    • Molecular signal partitioning ANKRD1 between compartments not defined
    • Durability/safety of import blockade untested
  22. 2024 Medium

    Connected ANKRD1 to integrin/FAK-based motility and myoblast fate via transcriptional repression of integrin genes and lamellipodial talin-1 colocalization.

    Evidence siRNA/overexpression, RNA-seq, Itga6 reporter, FAK phosphorylation, and immunofluorescence co-localization in myoblasts and renal carcinoma cells

    PMID:38988048 PMID:40362467

    Open questions at the time
    • Whether nuclear repression and lamellipodial localization are the same pool unclear
    • Direct ANKRD1–talin-1 binding not biochemically resolved
  23. 2024 Medium

    Showed ANKRD1 regulates cardiomyocyte cell cycle and regeneration through cyclin D1.

    Evidence Cardiomyocyte-specific knockdown/overexpression in neonatal apical resection and adult MI models with cyclin D1 analysis

    PMID:39299480

    Open questions at the time
    • Direct link between ANKRD1 and cyclin D1 regulation not mechanistically defined
    • Translatability to human cardiac repair untested
  24. 2024 Medium

    Identified post-transcriptional control of ANKRD1 by RBMS1-mediated mRNA stabilization during senescence.

    Evidence ASO pulldown-MS, RIP, mRNA half-life, RBMS1 manipulation and heterologous reporter

    PMID:38769646

    Open questions at the time
    • Functional output of senescence-associated ANKRD1 induction not defined
    • RBMS1 binding site fine-mapping incomplete

Open questions

Synthesis pass · forward-looking unresolved questions
  • It remains unknown what molecular switch governs ANKRD1 partitioning between its sarcomeric/cytosolic structural role and its nuclear transcriptional role, and which E3 ligase enforces its PEST-dependent turnover.
  • Compartment-partitioning signal unidentified
  • E3 ligase for ANKRD1 degradation unknown
  • Unifying logic across muscle, fibroblast, cancer and ferroptosis roles unresolved

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0140110 transcription regulator activity 6 GO:0008092 cytoskeletal protein binding 3 GO:0098772 molecular function regulator activity 3 GO:0003677 DNA binding 2
Localization
GO:0005634 nucleus 4 GO:0005856 cytoskeleton 4 GO:0005829 cytosol 2
Pathway
R-HSA-392499 Metabolism of proteins 3 R-HSA-397014 Muscle contraction 3 R-HSA-74160 Gene expression (Transcription) 3 R-HSA-162582 Signal Transduction 2 R-HSA-5357801 Programmed Cell Death 1
Complex memberships
ANKRD1/ERK1/2/GATA4 sarcomeric signaling complex

Evidence

Reading pass · 28 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2009 ANKRD1/CARP physically interacts with the N2A domain of titin/connectin and with myopalladin in cardiomyocytes; HCM-associated missense mutations (Pro52Ala, Thr123Met, Ile280Val) increase binding of CARP to both titin/connectin and myopalladin, and cause abnormal localization of CARP in neonatal rat cardiomyocytes. Co-immunoprecipitation, cellular localization in neonatal rat cardiomyocytes with myc-tagged mutant CARP Journal of the American College of Cardiology High 19608031
2009 DCM-associated ANKRD1 mutations (M184I and P105S) abolish or reduce binding of CARP to Talin-1, and M184I also disrupts binding to FHL2, as measured by yeast two-hybrid; these mutations alter stretch-mediated gene expression without changing intracellular localization of mutant CARP proteins. Yeast two-hybrid, quantitative real-time RT-PCR of stretch-induced gene expression in myoblastoid cell lines Journal of the American College of Cardiology Medium 19608030
2009 DCM-associated ANKRD1 mutant proteins (sequenced from 231 DCM patients) show significantly reduced transcriptional repressor activity in reporter gene assays and greater phenylephrine-induced hypertrophy when expressed in neonatal rat cardiomyocytes, indicating loss-of-function for transcriptional repression. Reporter gene assay (transfection in neonatal rat cardiomyocytes), hypertrophy assay European heart journal Medium 19525294
2008 A TAPVR-associated missense mutation in ANKRD1 enhances protein stability (resistance to calpain-mediated degradation) and increases its transcriptional repression activity on the ANF promoter. In vitro calpain-mediated degradation assay, reporter gene analysis in transfected HeLa cells Human mutation Medium 18273862
2009 ANKRD1 protein levels are regulated by 26S proteasome-mediated degradation; a PEST motif within ANKRD1 is critical for this degradation, though other degrons also contribute. Proteasome inhibitor treatment, PEST motif mutagenesis, pulse-chase analysis FEBS letters Medium 19589340
2010 ANKRD1/CARP physically interacts with the tumor suppressor p53 both in vivo and in vitro, and functions as a transcriptional co-activator that moderately upregulates p53 activity; p53 in turn acts as an upstream effector that upregulates the proximal ANKRD1 promoter. Protein array, co-immunoprecipitation (in vivo and in vitro), reporter gene assay (promoter activity) Archives of biochemistry and biophysics Medium 20599664
2015 ANKRD1 is part of a sarcomeric signaling complex with ERK1/2 and GATA4 in neonatal rat ventricular myocytes; phenylephrine treatment induces ERK1/2 and GATA4 phosphorylation and nuclear translocation of the ANKRD1/ERK/GATA4 complex. Knockdown of Ankrd1 attenuates ERK1/2 and GATA4 phosphorylation and prevents PE-induced cardiomyocyte growth. Ankrd1 null mice fail to develop PE-induced cardiac hypertrophy but develop normal hypertrophy in response to pressure overload (TAC). Co-immunoprecipitation, siRNA knockdown, adrenergic agonist stimulation assays, Ankrd1 knockout mouse with PE infusion and TAC Cardiovascular research High 25770146
2012 GATA4 acts upstream of ANKRD1 by activating the proximal CARP/ANKRD1 promoter; CARP/ANKRD1 knockdown inhibits myofilament gene transcription and induces sarcomere disarray; CARP depletion abolishes GATA4 overexpression-mediated rescue of doxorubicin-induced sarcomere disorganization, demonstrating co-dependent roles for GATA4 and CARP in sarcomere gene expression and structural maintenance. Co-transfection reporter assay, siRNA knockdown, adenoviral overexpression, doxorubicin treatment in cardiomyocytes PloS one Medium 22532871
2005 ANKRD1 selectively binds cardiac calsequestrin-2 (CASQ2) in heart extracts, confirmed by pull-down, blot-overlay, and co-immunoprecipitation; five non-overlapping binding sequences for CASQ2 were mapped on ANKRD1, and three ANKRD1-binding peptides were identified on CASQ2; endogenous ANKRD1 and CASQ2 are co-enriched in cardiac Purkinje cells. Pull-down from heart tissue extracts, blot-overlay assay, co-immunoprecipitation, peptide mapping, immunohistochemistry Journal of molecular and cellular cardiology High 15698842
2015 ANKRD1 binds the p50 subunit of NF-κB (confirmed by co-immunoprecipitation) and inhibits TNFα-induced NF-κB transcriptional activity in C2C12 myoblasts; ANKRD1 also binds chromatin at an NF-κB binding site in the ANKRD2 promoter in a NF-κB-dependent manner, providing feedback inhibition of NF-κB signaling. Co-immunoprecipitation, siRNA knockdown, overexpression, NF-κB reporter assay, ChIP assay Biochemical and biophysical research communications Medium 26102030
2014 ANKRD1 acts as a transcriptional repressor of MMP13 via the AP-1 site; ANKRD1 associates with nucleolin (by yeast two-hybrid and co-immunoprecipitation); deletion of Ankrd1 elevates MMP13 mRNA and protein; ChIP shows greater c-Jun binding to the MMP13 AP-1 site in Ankrd1-null fibroblasts; ANKRD1 also represses MMP10. Yeast two-hybrid, co-immunoprecipitation, EMSA, ChIP, promoter activity assay, qPCR, protein analysis in Ankrd1-/- mice Molecular and cellular biology High 24515436
2014 Global deletion of Ankrd1 impairs dermal fibroblast spreading and migration on collagen and fibronectin, abolishes contraction of 3D collagen gels, and delays wound closure in vivo; adenoviral re-expression of ANKRD1 restores collagen gel contraction, actin fiber organization, and rescues ischemic skin flap necrosis. Global Ankrd1 KO mouse (Sox2-cre), fibroblast migration and spreading assays, 3D collagen gel contraction, adenoviral reconstitution, excisional wound and ischemic flap models The American journal of pathology High 25452119
2013 ANKRD1 binds the androgen receptor (AR) (by co-immunoprecipitation) and acts as a transcriptional repressor of AR-mediated gene expression; testosterone reduces Ankrd1 mRNA ~50% in L6.AR myoblasts; Ankrd1 overexpression blocks testosterone-induced reporter gene activity and modulates expression of MEF2d, myogenin, p21, and TnnI1 downstream of AR. Co-immunoprecipitation, reporter gene assay (ARE-Luc, MAFbx-Luc), qPCR of testosterone-regulated genes Biochemical and biophysical research communications Medium 23811403
2013 HCM-associated ANKRD1 mutations have distinct functional consequences in engineered heart tissues: T123M produces a gain-of-function with higher contractile force and velocities and correct sarcomere incorporation; P52A and I280V are highly unstable, excluded from the sarcomere, and rapidly degraded by the proteasome; proteasome inhibition stabilizes P52A and I280V, enabling sarcomere incorporation, and I280V then produces prolonged relaxation (dominant-negative effect). Adeno-associated virus gene transfer into engineered heart tissues, contractile parameter analysis, proteasome inhibitor (epoxomicin) treatment Basic research in cardiology Medium 23572067
2011 ANKRD1 interacts with desmin in smooth muscle cells; siRNA knockdown of desmin upregulates Ankrd1 expression via activation of the Akt/IKKα/IκBα/NF-κB signaling cascade; NF-κB directly binds the Ankrd1 promoter to drive its transcription as shown by luciferase reporter assay. siRNA knockdown, Western blot for pathway phosphorylation, pharmacological inhibitors of Akt/IKK/NF-κB, siRNA against p50/p65, luciferase reporter assay FASEB journal Medium 22085644
2017 ANKRD1 is a YAP1 target gene induced by RASSF1A co-expression; ANKRD1 physically interacts with p53, induces TP53, BAX, and CDKN1A expression, destabilizes MDM2, and reduces cancer cell colony formation in a p53-dependent manner. Reporter/expression assays, co-immunoprecipitation (ANKRD1–p53 interaction), colony formation assay, gene expression analysis Oncotarget Medium 29179447
2015 ERK5, but not ERK1/2, induces Ankrd1 expression in PC12 adrenal cells; Ankrd1 stabilizes tyrosine hydroxylase (TH) protein (without changing TH mRNA), reduces TH ubiquitination, and is required for catecholamine biosynthesis during neural differentiation. Microarray with ERK5/ERK1/2-specific inhibitors, siRNA knockdown, ubiquitination assay, catecholamine biosynthesis measurement Cellular signalling Medium 26739108
2020 ANKRD1 overexpression in mouse myocardium causes sinus venosus defect during development through impaired remodeling; adult transgenic hearts develop progressive diastolic dysfunction with impaired lusitropism, sarcomere disassembly, and altered titin gene expression; embryonic overexpression transiently activates GATA4-Nkx2.5 transcription. ANKRD1 has dynamic nucleo-sarcomeric localization in developing cardiomyocytes. Transgenic mouse overexpression (myocardium-specific), histological analysis, hemodynamic measurements, myofibrillar functional assays, transcriptional profiling Cardiovascular research High 31688894
2024 Nuclear AGO2 activates ANKRD1 transcription in failing cardiomyocytes; nuclear ANKRD1 overexpression exacerbates cardiac remodeling by inducing MYH7 (pathological), while cytosolic ANKRD1 appears cardioprotective; ivermectin and an ANKRD1 nuclear localization signal mimetic peptide (ANPep) block ANKRD1 nuclear import and improve cardiac function in TAC-induced heart failure mice. Recombinant AAV9 overexpression (nuclear vs. cytosolic AGO2/ANKRD1), TAC mouse model, mechanistic reporter assays, pharmacological intervention with ivermectin and ANPep Molecular therapy Medium 38475992
2024 ANKRD1 promotes ACSL3 degradation by facilitating TRIM25-mediated K63-linked ubiquitination of ACSL3, thereby amplifying lipid peroxidation and ferroptosis during renal ischemia-reperfusion injury; knockdown of ANKRD1 in mouse kidneys (rAAV9) reduces renal damage and ferroptosis. Immunoprecipitation-mass spectrometry (interactome), Co-IP, proximity ligation assay, ubiquitination assay, rAAV9-mediated knockdown in vivo, cell viability and lipid peroxidation assays Clinical and translational medicine High 39285846
2024 ANKRD1 is a mesenchymal-specific transcriptional coregulator under direct androgen receptor (AR) negative control; ANKRD1 drives cancer-associated fibroblast (CAF) activation by binding regulatory regions of myofibroblast CAF effector genes and promoting c-JUN and FOS (AP-1) association; targeting ANKRD1 disrupts AP-1 complex formation and reverses CAF activation in an orthotopic skin cancer model. Chromatin immunoprecipitation (ChIP), Co-IP for AP-1 complex, siRNA/knockdown, AR overexpression/loss, orthotopic mouse tumor model Nature communications High 38310103
2024 ANKRD1 knockdown in C2C12 myoblasts decreases proliferation but increases differentiation; mechanistically, Ankrd1 represses the Itga6 promoter (shown by dual-luciferase reporter assay), and its knockdown upregulates ITGA6, leading to enhanced FAK phosphorylation and activation of the FAK/Rho-GTPase/F-actin pathway. siRNA knockdown, overexpression, RNA-seq, dual-luciferase reporter assay for Itga6 promoter, FAK phosphorylation assay Journal of cellular physiology Medium 38988048
2024 ANKRD1 promotes lamellipodia formation and cell motility in clear cell renal cell carcinoma cells; ANKRD1 colocalizes with F-actin and talin-1 in lamellipodia upon phorbol ester stimulation; ANKRD1 depletion represses talin-1-mediated integrin pathway activation and reduces lamellipodia formation. siRNA knockdown, overexpression, immunofluorescence co-localization, migration assay, integrin pathway activation analysis International journal of molecular sciences Medium 40362467
2024 RBMS1 RNA-binding protein stabilizes ANKRD1 mRNA during early senescence; RBMS1 relocates from nucleus to cytoplasm after etoposide treatment, binds a region proximal to the ANKRD1 coding sequence, and silencing RBMS1 reduces while overexpressing RBMS1 enhances ANKRD1 mRNA half-life. Antisense oligomer pulldown with mass spectrometry, ribonucleoprotein immunoprecipitation, mRNA half-life measurement, RBMS1 siRNA and overexpression, heterologous reporter assay Molecular and cellular biology Medium 38769646
2024 Ankrd1 regulates cardiomyocyte cell cycle and cardiac regeneration, at least in part through cyclin D1; cardiomyocyte-specific Ankrd1 knockdown inhibits myocardial regeneration after apical resection in neonatal mice, and cardiomyocyte-specific overexpression promotes cardiac repair after adult myocardial infarction. Ankrd1 cardiomyocyte-specific knockdown and overexpression, neonatal apical resection model, adult MI model, cyclin D1 mechanistic analysis European journal of pharmacology Medium 39299480
2012 The 26S proteasome is the dominant regulator of ANKRD1/CARP degradation in both adult rat ventricular myocytes and human microvascular endothelial cells; ANKRD1/CARP half-life is significantly longer in cardiomyocytes (hours) than in endothelial cells (minutes), and higher endothelial cell density decreases ANKRD1 protein without affecting mRNA. Proteasome inhibitor treatment, protein half-life measurement (pulse-chase), cell density manipulation Biochemical and biophysical research communications Medium 22892129
2023 ANKRD1 regulates ferroptosis in HK-2 renal tubular cells through the p53/SLC7A11 signaling pathway; silencing or overexpression of ANKRD1 modulates SLC7A11 and GPX4 expression and the extent of ferroptosis induced by CaOx crystals. Lentiviral ANKRD1 silencing and overexpression, Western blot for ferroptosis markers (SLC7A11, GPX4, ACSL4), Fe2+ accumulation assay Biochimica et biophysica acta. Molecular cell research Low 36907445
2023 ANKRD1 promotes osteogenic differentiation of BMSCs by modulating CAV3 expression through reduction of CAV3 ubiquitination, thereby activating Wnt/β-catenin signaling; CAV3 knockdown abolishes the pro-osteogenic effect of ANKRD1 overexpression. Lentiviral ANKRD1 overexpression and knockdown in BMSCs, ALP activity, osteogenic gene qPCR, Wnt/β-catenin pathway analysis, CAV3 ubiquitination assay, epistasis (CAV3 knockdown rescue) Biochimica et biophysica acta. Molecular basis of disease Medium 36958710

Source papers

Stage 0 corpus · 52 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2009 Cardiac ankyrin repeat protein gene (ANKRD1) mutations in hypertrophic cardiomyopathy. Journal of the American College of Cardiology 123 19608031
2009 ANKRD1, the gene encoding cardiac ankyrin repeat protein, is a novel dilated cardiomyopathy gene. Journal of the American College of Cardiology 115 19608030
2019 RREB1-induced upregulation of the lncRNA AGAP2-AS1 regulates the proliferation and migration of pancreatic cancer partly through suppressing ANKRD1 and ANGPTL4. Cell death & disease 95 30814490
2001 Yeast ERV2p is the first microsomal FAD-linked sulfhydryl oxidase of the Erv1p/Alrp protein family. The Journal of biological chemistry 87 11313344
2015 Targeted inhibition of ANKRD1 disrupts sarcomeric ERK-GATA4 signal transduction and abrogates phenylephrine-induced cardiomyocyte hypertrophy. Cardiovascular research 66 25770146
2009 Mutations in the ANKRD1 gene encoding CARP are responsible for human dilated cardiomyopathy. European heart journal 65 19525294
2010 A novel role for cardiac ankyrin repeat protein Ankrd1/CARP as a co-activator of the p53 tumor suppressor protein. Archives of biochemistry and biophysics 62 20599664
2014 Inhibition of ANKRD1 sensitizes human ovarian cancer cells to endoplasmic reticulum stress-induced apoptosis. Oncogene 52 24531715
2012 Disruption of a GATA4/Ankrd1 signaling axis in cardiomyocytes leads to sarcomere disarray: implications for anthracycline cardiomyopathy. PloS one 49 22532871
2008 Transcriptional deregulation and a missense mutation define ANKRD1 as a candidate gene for total anomalous pulmonary venous return. Human mutation 47 18273862
2017 The tumor suppressor RASSF1A induces the YAP1 target gene ANKRD1 that is epigenetically inactivated in human cancers and inhibits tumor growth. Oncotarget 44 29179447
2014 Global deletion of Ankrd1 results in a wound-healing phenotype associated with dermal fibroblast dysfunction. The American journal of pathology 43 25452119
2013 Impact of ANKRD1 mutations associated with hypertrophic cardiomyopathy on contraction parameters of engineered heart tissue. Basic research in cardiology 40 23572067
2008 Ankyrin repeat domain 1, ANKRD1, a novel determinant of cisplatin sensitivity expressed in ovarian cancer. Clinical cancer research : an official journal of the American Association for Cancer Research 40 18980987
2015 ANKRD1 modulates inflammatory responses in C2C12 myoblasts through feedback inhibition of NF-κB signaling activity. Biochemical and biophysical research communications 39 26102030
2009 Porcine muscle sensory attributes associate with major changes in gene networks involving CAPZB, ANKRD1, and CTBP2. Functional & integrative genomics 39 19597856
2014 ANKRD1 acts as a transcriptional repressor of MMP13 via the AP-1 site. Molecular and cellular biology 37 24515436
2015 Induction of Ankrd1 in Dilated Cardiomyopathy Correlates with the Heart Failure Progression. BioMed research international 34 25961010
2002 Accumulation of the mitochondrial form of the sulphydryl oxidase Erv1p/Alrp during the early stages of spermatogenesis. The Journal of experimental biology 33 12089204
2020 Myocardial overexpression of ANKRD1 causes sinus venosus defects and progressive diastolic dysfunction. Cardiovascular research 31 31688894
2024 ANKRD1 is a mesenchymal-specific driver of cancer-associated fibroblast activation bridging androgen receptor loss to AP-1 activation. Nature communications 30 38310103
2005 ANKRD1 specifically binds CASQ2 in heart extracts and both proteins are co-enriched in piglet cardiac Purkinje cells. Journal of molecular and cellular cardiology 30 15698842
2011 Alrp, a survival factor that controls the apoptotic process of regenerating liver after partial hepatectomy in rats. Free radical research 28 21291353
2011 Loss of desmin triggers mechanosensitivity and up-regulation of Ankrd1 expression through Akt-NF-κB signaling pathway in smooth muscle cells. FASEB journal : official publication of the Federation of American Societies for Experimental Biology 25 22085644
2009 Intracellular ANKRD1 protein levels are regulated by 26S proteasome-mediated degradation. FEBS letters 25 19589340
2023 Ferroptosis in calcium oxalate kidney stone formation and the possible regulatory mechanism of ANKRD1. Biochimica et biophysica acta. Molecular cell research 23 36907445
2021 Baoyuan decoction (BYD) attenuates cardiac hypertrophy through ANKRD1-ERK/GATA4 pathway in heart failure after acute myocardial infarction. Phytomedicine : international journal of phytotherapy and phytopharmacology 21 34157504
2009 Intron retention generates ANKRD1 splice variants that are co-regulated with the main transcript in normal and failing myocardium. Gene 19 19341785
2023 ANKRD1 activates the Wnt signaling pathway by modulating CAV3 expression and thus promotes BMSC osteogenic differentiation and bone formation in ovariectomized mice. Biochimica et biophysica acta. Molecular basis of disease 18 36958710
2015 ERK5 induces ankrd1 for catecholamine biosynthesis and homeostasis in adrenal medullary cells. Cellular signalling 17 26739108
2024 Nuclear AGO2 promotes myocardial remodeling by activating ANKRD1 transcription in failing hearts. Molecular therapy : the journal of the American Society of Gene Therapy 15 38475992
2022 Storax Attenuates Cardiac Fibrosis following Acute Myocardial Infarction in Rats via Suppression of AT1R-Ankrd1-P53 Signaling Pathway. International journal of molecular sciences 15 36361958
2013 Ankrd1 is a transcriptional repressor for the androgen receptor that is downregulated by testosterone. Biochemical and biophysical research communications 15 23811403
2024 ANKRD1 aggravates renal ischaemia‒reperfusion injury via promoting TRIM25-mediated ubiquitination of ACSL3. Clinical and translational medicine 13 39285846
2012 26S proteasome regulation of Ankrd1/CARP in adult rat ventricular myocytes and human microvascular endothelial cells. Biochemical and biophysical research communications 12 22892129
2024 Ankrd1 inhibits the FAK/Rho-GTPase/F-actin pathway by downregulating ITGA6 transcriptional to regulate myoblast functions. Journal of cellular physiology 9 38988048
2021 LncRNA RGMB-AS1 up-regulates ANKRD1 Through Competitively Sponging miR-3614-5p to Promote OSA Cell Proliferation and Invasion. Archives of medical research 9 34583851
2024 Increased ANKRD1 Levels in Early Senescence Mediated by RBMS1-Elicited ANKRD1 mRNA Stabilization. Molecular and cellular biology 7 38769646
2024 ANKRD1 Promotes Breast Cancer Metastasis by Activating NF-κB-MAGE-A6 Pathway. Cancers 6 39409926
2024 ANKRD1 expression is aberrantly upregulated in the mdm mouse model of muscular dystrophy and induced by stretch through NFκB. Journal of muscle research and cell motility 5 38683293
2024 Integrating miRNA and full-length transcriptome profiling to elucidate the mechanism of muscle growth in Muscovy ducks reveals key roles for miR-301a-3p/ANKRD1. BMC genomics 4 38575872
2025 Ankrd1 as a potential biomarker for the transition from acute kidney injury to chronic kidney disease. Scientific reports 3 39920300
2022 Genetic Ablation of Ankrd1 Mitigates Cardiac Damage during Experimental Autoimmune Myocarditis in Mice. Biomolecules 3 36551326
2025 Ankrd1 Promotes Lamellipodia Formation and Cell Motility via Interaction with Talin-1 in Clear Cell Renal Cell Carcinoma. International journal of molecular sciences 2 40362467
2024 Ankrd1 regulates endogenous cardiac regeneration in mice by modulating cyclin D1. European journal of pharmacology 2 39299480
2021 Clinical and pathohistological characteristics of Alport spectrum disorder caused by COL4A4 mutation c.193-2A>C: a case series. Croatian medical journal 2 34212557
2015 Hb G-Waimanalo [A1] [α64(E13)Asp→Asn; HBA1: c.193 G > A] with Decreased Oxygen Affinity. Hemoglobin 1 26291968
2026 ANKRD1 sustains a neurogenic BMSC niche and counters cognitive aging. International journal of oral science 0 41764190
2026 ANKRD1 expression and functional mechanism in stomach adenocarcinoma. Clinical & translational oncology : official publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico 0 41770518
2026 Yifei Sanjie pill combined with gefitinib reduces the progression of EGFR-TKIs-resistant non-small cell lung cancer via YAP/ANKRD1 axis. Phytomedicine : international journal of phytotherapy and phytopharmacology 0 41865688
2025 DNA-methylation-mediated silencing of lncRNA PP7080 promotes the progression of gastric cancer by regulating ANKRD1 expression. Translational oncology 0 40516143
2024 Molecular characterization of ANKRD1 in rhabdomyosarcoma cell lines: expression, localization, and proteasomal degradation. Histochemistry and cell biology 0 38396247

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