Affinage

CCAR2

Cell cycle and apoptosis regulator protein 2 · UniProt Q8N163

Length
923 aa
Mass
102.9 kDa
Annotated
2026-06-09
37 papers in source corpus 22 papers cited in narrative 22 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

CCAR2 (DBC1) is a multifunctional nuclear scaffold that integrates deacetylase regulation, DNA repair, and nuclear-receptor signaling to control cell survival and genome stability (PMID:24126058, PMID:36442094, PMID:17473282). Its best-defined activity is as an endogenous inhibitor of the SIRT1 deacetylase: direct CCAR2-SIRT1 binding restrains SIRT1, and this brake is set by post-translational marks and competing binders—hMOF-mediated acetylation of CCAR2 at K112/K215 blocks SIRT1 binding while DNA-damage signaling reduces this acetylation to strengthen the interaction (PMID:24126058), and nuclear GAPDH can displace CCAR2 from SIRT1 to drive SIRT1-dependent LC3B deacetylation and autophagy (PMID:33459133). By gating SIRT1, CCAR2 controls deacetylation of downstream effectors including p53, with CCAR2 accumulation increasing p53 acetylation, stability, and apoptosis; CCAR2 levels are themselves limited by UBE4B-mediated ubiquitination and proteasomal degradation (PMID:42074320). In DNA repair, CCAR2 suppresses DNA double-strand break end-resection as a functional component of the 53BP1-RIF1-Shieldin pathway, acting downstream of Shieldin through its S1-like RNA-binding domain to favor NHEJ over homologous recombination (PMID:36442094, PMID:27503537), and it is also required for Chk2-dependent KAP1 phosphorylation needed to repair heterochromatic breaks (PMID:26158765). CCAR2 additionally functions as a ligand-independent co-regulator and stabilizer of nuclear receptors through N-terminal domain interactions, binding and stabilizing unliganded ERα, stabilizing androgen receptor against degradation, and attenuating LXRα by competing with SIRT1 (PMID:17473282, PMID:26249023, PMID:25661920), and it co-activates Wnt/β-catenin signaling (PMID:34624572). Beyond the nucleus, CCAR2 localizes to mitochondria and forms a pro-survival complex with Hsp60 under mitochondrial stress (PMID:28254432), and it regulates mitotic progression via spatiotemporal control of Aurora B (PMID:35672287). The CCAR2-SIRT1 interface is a tractable pharmacological target, disrupted by small molecules including genistein and ginsenoside Rf to restore SIRT1 activity (PMID:41775214, PMID:41825964).

Mechanistic history

Synthesis pass · year-by-year structured walk · 19 steps
  1. 2007 High

    Established CCAR2 as a ligand-independent nuclear-receptor co-regulator by showing its N-terminus directly binds and stabilizes unliganded ERα, linking it to hormone-independent breast cancer cell survival.

    Evidence In vitro binding, co-IP, and siRNA with apoptosis readout in ERα-positive breast cancer cells

    PMID:17473282

    Open questions at the time
    • Did not define the structural basis of the N-terminal-ERα interface
    • Did not connect ERα stabilization to CCAR2's SIRT1-inhibitory role
  2. 2013 High

    Defined how the CCAR2-SIRT1 brake is regulated, showing hMOF acetylation at K112/K215 blocks SIRT1 binding and DNA damage reverses this to enhance the inhibitory complex.

    Evidence Mass spectrometry, in vitro acetyltransferase assay, mutagenesis, reciprocal co-IP, and apoptosis readout

    PMID:24126058

    Open questions at the time
    • Did not establish in vivo stoichiometry of the acetylation switch
    • Upstream signals coupling ATM to hMOF inhibition incompletely defined
  3. 2015 Medium

    Placed CCAR2 in heterochromatic DSB repair by showing it is required for Chk2-dependent KAP1 phosphorylation and heterochromatin relaxation, separable from euchromatic repair.

    Evidence CCAR2 knockout cells, foci immunofluorescence, phospho-western, and HP1β epistasis

    PMID:26158765

    Open questions at the time
    • Mechanism by which CCAR2 promotes Chk2 activation not defined
    • Single lab without reciprocal genetic confirmation
  4. 2015 Medium

    Extended CCAR2's nuclear-receptor co-regulation beyond ERα, showing direct N-terminal binding to LXRα and AR with opposing functional outcomes (LXRα attenuation via SIRT1 competition; AR stabilization against degradation).

    Evidence GST pull-down, competitive co-IP, ubiquitination assay, and siRNA in HepG2 and osteosarcoma cells

    PMID:25661920 PMID:26249023

    Open questions at the time
    • Why CCAR2 stabilizes some receptors but attenuates others not resolved
    • Receptor selectivity determinants on the N-terminal domain unknown
  5. 2016 High

    Identified CCAR2 in an unbiased screen as an inhibitor of DNA end-resection that biases repair toward NHEJ by antagonizing CtIP, establishing a genome-wide functional anchor for its repair role.

    Evidence Genome-wide esiRNA SeeSaw Reporter screen with RPA/ssDNA resection validation

    PMID:27503537

    Open questions at the time
    • Did not yet place CCAR2 in the 53BP1-Shieldin axis
    • Molecular contact with the resection machinery not defined here
  6. 2016 Medium

    Revealed a cancer-selective signaling role in which CCAR2 loss upregulates TRB3 to inhibit AKT Ser473 phosphorylation, causing G1/S arrest.

    Evidence siRNA, western blot of AKT/GSK3β, TRB3-AKT co-IP, and cell cycle analysis

    PMID:27809307

    Open questions at the time
    • How CCAR2 transcriptionally controls TRB3 is unclear
    • Cancer-cell specificity not mechanistically explained
  7. 2017 Medium

    Showed CCAR2 has an extranuclear, mitochondrial function, forming a stress-induced complex with Hsp60 that supports membrane potential and survival.

    Evidence Affinity purification, co-IP, mitochondrial fractionation, JC-1, and apoptosis assays under rotenone stress

    PMID:28254432

    Open questions at the time
    • Mechanism by which CCAR2-Hsp60 sustains membrane potential undefined
    • Relationship between mitochondrial and nuclear CCAR2 pools unknown
  8. 2019 Medium

    Defined an acetyl-switch governing CCAR2's Wnt co-activator role, where N-terminal acetylation recruits BET/BRD9 readers and weakens HDAC3 and β-catenin binding.

    Evidence Domain arrays, pull-downs, acetylation mimics, and a tumor prevention model with JQ1/sulforaphane synergy

    PMID:30643017

    Open questions at the time
    • Enzyme responsible for the relevant N-terminal acetylation in this context not pinned down
    • Direct structural basis of reader recognition not shown
  9. 2019 Low

    Linked the CCAR2-Hsp60 complex to anti-apoptotic survivin expression in neuroblastoma cells.

    Evidence siRNA co-depletion with survivin western/RT-PCR and apoptosis assays

    PMID:30609639

    Open questions at the time
    • No direct biochemical interaction between CCAR2 and survivin pathway components shown
    • Single lab, correlative expression readout only
  10. 2021 High

    Showed CCAR2 release from SIRT1 can be triggered by nuclear GAPDH redistribution, activating SIRT1-mediated LC3B deacetylation and autophagy to restrict intracellular M. tuberculosis.

    Evidence Reciprocal co-IP, PLA, GAPDH active-site mutant, LC3B assays, and bacterial CFU

    PMID:33459133

    Open questions at the time
    • Physiological stimuli driving GAPDH-CCAR2 engagement beyond H2S not delineated
    • Direct CCAR2-GAPDH binding interface not mapped
  11. 2021 Medium

    Identified CCAR2 as a tissue-specific subunit of the CECR2 (CERF) chromatin remodeling complex in ES cells, broadening its chromatin functions.

    Evidence Mass spectrometry of CECR2 immunoprecipitates from ES cells and testes with co-IP validation

    PMID:34197713

    Open questions at the time
    • Functional consequence of CCAR2 within CERF undefined
    • Determinants of tissue-specific incorporation unknown
  12. 2021 Medium

    Established CCAR2 as a Wnt/β-catenin co-activator driving SPARC to promote osteosarcoma malignancy.

    Evidence siRNA, transcriptomics, SPARC rescue, Wnt reporter, and xenograft

    PMID:34624572

    Open questions at the time
    • Direct promoter-level mechanism of SPARC induction not shown
    • Relation to the BET/BRD9 acetyl switch not tested
  13. 2022 High

    Resolved CCAR2's resection-suppressing activity into the 53BP1-RIF1-Shieldin pathway, acting downstream of Shieldin via its S1-like RNA-binding domain to promote NHEJ.

    Evidence Reciprocal co-IP, domain-deletion mutagenesis, CRISPR KO, RPA/RAD51 assays, epistasis, and PARP-inhibitor rescue in BRCA1−/−SHLD2−/− cells

    PMID:36442094

    Open questions at the time
    • RNA ligand (if any) bound by the S1-like domain not identified
    • Structural basis of Shieldin engagement undefined
  14. 2022 Medium

    Demonstrated a mitotic role for CCAR2 in spatiotemporal control of Aurora B, required for proper centromeric cohesion, checkpoint signaling, and faithful segregation.

    Evidence siRNA/KO, live-cell imaging, Aurora B/BUBR1 immunofluorescence, and abscission checkpoint assays

    PMID:35672287

    Open questions at the time
    • Whether CCAR2 directly binds or regulates Aurora B not established
    • Connection to its nuclear scaffold functions unclear
  15. 2025 Low

    Connected CCAR2 to oxidative-stress cytokine control, with its depletion activating AP-1 and IL-8 in cervical cancer cells.

    Evidence siRNA, H2O2 treatment, IL-8 ELISA/RT-PCR, AP-1 reporter, and patient tissue correlation

    PMID:29416683

    Open questions at the time
    • No direct binding linking CCAR2 to the AP-1/IL-8 axis demonstrated
    • Single lab, pathway placement inferred from reporter only
  16. 2025 Medium

    Showed CCAR2 protein stability is controlled by a TFPI2-BRCC3 deubiquitination axis and that CCAR2 stabilizes GADD45A mRNA to inhibit HR and sensitize HCC to sorafenib.

    Evidence RNA-IP, ChIP, co-IP (TFPI2-BRCC3-CCAR2), ubiquitination assay, organoids and in vivo models

    PMID:40765823

    Open questions at the time
    • Direct CCAR2-GADD45A mRNA binding determinants not mapped
    • Interplay with the UBE4B degradation pathway untested
  17. 2025 Low

    Reported a cytoplasmic CCAR2-p30 interaction in which CCAR2 supports African swine fever virus replication.

    Evidence Mass spectrometry, co-IP, co-localization, siRNA, and viral replication assay

    PMID:39919500

    Open questions at the time
    • Single co-IP without reciprocal/structural validation
    • Mechanism by which CCAR2 aids replication unknown
  18. 2026 Medium

    Identified UBE4B as an E3/E4 ligase that ubiquitinates CCAR2 for degradation, linking CCAR2 turnover to SIRT1 activity and p53 acetylation/apoptosis.

    Evidence OUT substrate screen, in vitro ubiquitination, SIRT1 activity assay, p53 acetylation western, and rescue epistasis

    PMID:42074320

    Open questions at the time
    • Relative contribution of CCAR2 versus direct p53 degradation by UBE4B context-dependent
    • Signals regulating UBE4B-CCAR2 targeting unknown
  19. 2026 Medium

    Validated the CCAR2-SIRT1 interface as a druggable target by showing distinct natural products disrupt the inhibitory complex to restore SIRT1-dependent deacetylation of p53, FXR, and pro-survival programs in liver disease.

    Evidence Affinity pull-down/MS, CETSA, docking, co-IP, substrate-acetylation assays, and liver-specific Ccar2 KO mouse models

    PMID:41775214 PMID:41825964

    Open questions at the time
    • Co-crystal structures of compound-bound CCAR2 not reported
    • Selectivity over other CCAR2 functions not assessed

Open questions

Synthesis pass · forward-looking unresolved questions
  • How CCAR2's diverse activities—SIRT1 inhibition, Shieldin-dependent resection control, nuclear-receptor stabilization, chromatin remodeling, mitotic regulation, and mitochondrial survival signaling—are coordinated within a single protein, and which are governed by shared post-translational switches, remains unresolved.
  • No integrated structural model linking CCAR2's domains to its multiple complexes
  • Switching between nuclear, mitochondrial, and repair pools not mechanistically explained
  • Whether the S1-like RNA-binding domain binds a defined RNA is unknown

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0098772 molecular function regulator activity 4 GO:0060090 molecular adaptor activity 3 GO:0140110 transcription regulator activity 3 GO:0003723 RNA binding 2
Localization
GO:0005634 nucleus 3 GO:0000228 nuclear chromosome 2 GO:0005739 mitochondrion 1
Pathway
R-HSA-162582 Signal Transduction 3 R-HSA-73894 DNA Repair 3 R-HSA-5357801 Programmed Cell Death 2 R-HSA-1640170 Cell Cycle 1 R-HSA-9612973 Autophagy 1
Partners
ARCTNNB1ESR1GAPDHHSPD1NR1H3SIRT1UBE4B
Complex memberships
53BP1-RIF1-Shieldin complexCCAR2-Hsp60 complexCCAR2-SIRT1 complexCECR2-containing remodeling factor (CERF) complex

Evidence

Reading pass · 22 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2007 DBC-1/CCAR2 amino terminus binds directly to the ERα hormone-binding domain in a ligand-independent manner, stabilizing unliganded ERα protein; antiestrogens (tamoxifen, ICI 182,780) and estrogen disrupt this interaction. RNAi-mediated DBC-1 depletion reduces unliganded ERα protein levels and promotes hormone-independent apoptosis of ERα-positive breast cancer cells. In vitro binding assay, co-immunoprecipitation, RNA interference (siRNA knockdown), apoptosis assays Molecular endocrinology High 17473282
2013 hMOF (MYST-family acetyltransferase) acetylates DBC1/CCAR2 on lysine residues K112 and K215; this acetylation inhibits DBC1 binding to SIRT1, thereby increasing SIRT1 deacetylase activity. SIRT1 in turn promotes DBC1 deacetylation, forming a negative-feedback loop. After DNA damage, ATM-dependent inhibition of hMOF binding to DBC1 reduces DBC1 acetylation and enhances DBC1–SIRT1 binding. A DBC1 acetylation-mimic mutant fails to promote apoptosis after DNA damage. Mass spectrometry, co-immunoprecipitation, in vitro acetyltransferase assay, site-directed mutagenesis, deacetylase activity assay, apoptosis assay Molecular and cellular biology High 24126058
2015 CCAR2 is required for Chk2-dependent phosphorylation of KAP1, a step needed for heterochromatin relaxation and repair of heterochromatic DNA double-strand breaks. CCAR2 knockout cells exhibit defective Chk2 activation, elevated KAP1 non-phosphorylation, and persistent DNA damage foci specifically in heterochromatin; euchromatic repair is unaffected. HP1β depletion rescues the repair defect. CCAR2 knockout cells, immunofluorescence (γH2AX/53BP1 foci), western blot (Chk2 and KAP1 phosphorylation), epistasis with HP1β depletion Oncotarget Medium 26158765
2015 CCAR2/DBC1 forms a complex with LXRα directly (amino terminus of CCAR2 binds the AF-2 domain of LXRα) in a ligand-independent manner, attenuating LXRα transcriptional activation. CCAR2 competes with SIRT1 for LXRα binding, blocking SIRT1-LXRα complex formation and consequently preventing SIRT1-mediated deacetylation of LXRα. Co-immunoprecipitation in HepG2 cells, in vitro GST pull-down, competitive immunoprecipitation, RNA interference, target gene expression assay The Journal of steroid biochemistry and molecular biology Medium 25661920
2015 DBC1/CCAR2 promotes stabilization of androgen receptor (AR) protein in osteosarcoma cells by preventing its proteasomal degradation; siRNA knockdown of DBC1 increases poly-ubiquitination and proteasome-mediated degradation of AR. siRNA knockdown, ubiquitination assay, proteasome inhibitor treatment, western blot, cell invasion and proliferation assays Scientific reports Medium 26249023
2016 CCAR2 inhibits DNA end resection at double-strand breaks, thereby suppressing homologous recombination (HR) and favouring non-homologous end joining (NHEJ); CCAR2 acts as an antagonist of CtIP-dependent resection. Identified via genome-wide esiRNA screen using the SeeSaw Reporter that distinguishes HR from NHEJ. Genome-wide esiRNA library screen (SeeSaw Reporter), fluorescence-based HR/NHEJ ratio assay, functional validation of resection by RPA and ssDNA detection Nature communications High 27503537
2016 CCAR2 loss inhibits AKT pathway activation specifically in cancer cells (not normal cells) by transcriptionally upregulating TRB3, which binds and inhibits phosphorylation of AKT at Ser473, leading to reduced GSK3β phosphorylation, G1/S arrest, and impaired cancer cell proliferation. siRNA knockdown, western blot (AKT/pAKT, GSK3β), RT-PCR and protein level measurement of TRB3, co-immunoprecipitation (TRB3–AKT binding), cell cycle analysis Cell death & disease Medium 27809307
2017 CCAR2 localizes to mitochondria and forms a complex with the mitochondrial chaperone Hsp60; this interaction increases upon rotenone-induced mitochondrial stress. CCAR2 and Hsp60 co-depletion disrupts mitochondrial membrane potential and promotes apoptosis, indicating the CCAR2–Hsp60 complex supports cell survival during mitochondrial stress. Affinity purification of CCAR2-containing complexes, co-immunoprecipitation, mitochondrial fractionation, mitochondrial membrane potential assay (JC-1), apoptosis assay, siRNA knockdown Biochemical and biophysical research communications Medium 28254432
2019 N-terminal acetylation of CCAR2 (induced by sulforaphane) diminishes its interactions with HDAC3 and β-catenin, interfering with Wnt co-activator functions. Acetyl-reader proteins BRD9 and BET family members recognise the CCAR2 acetylation sites, establishing a BET/BRD9 acetyl switch. BET inhibitor JQ1 synergizes with sulforaphane in colon cancer cells. Protein domain arrays, pull-down assays, co-immunoprecipitation, genetically encoded acetylation mimics, tumor prevention model Cancer research Medium 30643017
2019 CCAR2 and Hsp60 are both required for survivin expression in neuroblastoma cells; co-depletion of CCAR2 and Hsp60 downregulates survivin (IAP family member), promoting cancer cell death. siRNA knockdown of CCAR2 and Hsp60, western blot and RT-PCR for survivin, apoptosis assays International journal of molecular sciences Low 30609639
2021 Nuclear GAPDH (redistributed by H2S-induced sulfhydration of its active-site cysteine) interacts with CCAR2 in the nucleus, disrupting the inhibitory CCAR2–SIRT1 complex. This activates SIRT1, which deacetylates LC3B, promoting its cytoplasmic translocation and autophagy flux. The pathway restricts intracellular Mycobacterium tuberculosis growth. Co-immunoprecipitation, proximity ligation assay, nuclear fractionation, siRNA/overexpression, GAPDH active-site cysteine mutant, LC3B deacetylation/localization assay, bacterial CFU assay Autophagy High 33459133
2021 CCAR2 is a component of the CECR2-containing chromatin remodeling factor (CERF) complex in embryonic stem (ES) cells but not in the testis, indicating tissue-specific complex assembly. LUZP1 also joins the CERF complex in ES cells and appears to stabilize it. Mass spectrometry of CECR2 immunoprecipitates from ES cells and testes, co-immunoprecipitation validation Biochemistry and cell biology Medium 34197713
2021 CCAR2 acts as a co-activator of Wnt/β-catenin signaling in osteosarcoma cells to drive transcriptional upregulation of SPARC; knockdown of CCAR2 reduces Wnt/β-catenin target gene expression, and forced SPARC expression rescues the malignant phenotype of CCAR2-depleted cells. siRNA knockdown, transcriptomic profiling of CCAR2-KD cells, rescue experiments (SPARC overexpression), Wnt/β-catenin reporter assay, in vivo xenograft Biochemical and biophysical research communications Medium 34624572
2022 CCAR2 is a functional component of the 53BP1–RIF1–Shieldin pathway that restricts DNA double-strand break end-resection and promotes NHEJ. CCAR2 co-immunoprecipitates with the Shieldin complex; its S1-like RNA-binding domain is required for this interaction and for suppression of end-resection. CCAR2 acts downstream of Shieldin (CCAR2 KO delays resolution of Shieldin foci). FHA-domain-dependent targeting of CCAR2 to DSB sites re-sensitizes BRCA1−/−SHLD2−/− cells to PARP inhibitors. CCAR2 KO is epistatic with Shieldin KO. Co-immunoprecipitation, domain-deletion mutagenesis, CRISPR knockout, RPA/RAD51 loading assays, PARP inhibitor sensitivity assay, epistasis analysis, foci resolution assay Proceedings of the National Academy of Sciences of the United States of America High 36442094
2022 CCAR2 governs mitotic progression by spatiotemporally regulating Aurora B kinase activity; CCAR2-deficient cells show premature centromeric cohesion loss, spindle assembly checkpoint inactivation, lagging chromosomes, and activation of the abscission checkpoint, resulting in multilobulated nuclei. CCAR2 siRNA/knockout, live-cell imaging, immunofluorescence (Aurora B, pH3, BUBR1), chromosome segregation analysis, cytokinesis/abscission checkpoint assay Cell death & disease Medium 35672287
2025 CCAR2 negatively regulates IL-8 production in cervical cancer cells under oxidative stress; CCAR2 depletion activates AP-1 transcription factor, leading to upregulated IL-8 expression. siRNA knockdown, H2O2 treatment, ELISA and RT-PCR for IL-8, AP-1 reporter/activity assay, patient tissue correlation Oncotarget Low 29416683
2025 TFPI2 stabilizes CCAR2 protein by associating with the deubiquitinating enzyme BRCC3, preventing ubiquitination-mediated degradation of CCAR2. CCAR2 in turn stabilizes GADD45A mRNA (via RNA immunoprecipitation), promoting GADD45A-mediated DNA damage and inhibiting homologous recombination repair, thereby sensitizing HCC cells to sorafenib. RNA immunoprecipitation, chromatin immunoprecipitation, Co-immunoprecipitation (TFPI2–BRCC3–CCAR2), ubiquitination assay, HCC organoids and in vivo models International journal of biological sciences Medium 40765823
2025 ASFV p30 viral protein interacts with host CCAR2 (confirmed by co-immunoprecipitation), and both CCAR2 and MATR3 promote ASFV replication; ASFV infection upregulates CCAR2 expression in host cells. CCAR2 and p30 co-localize in the cytoplasm. Mass spectrometry, co-immunoprecipitation, co-localization (fluorescence microscopy), siRNA knockdown, viral replication assay Veterinary microbiology Low 39919500
2026 UBE4B (E3/E4 ubiquitin ligase) ubiquitinates CCAR2, promoting its proteasomal degradation. UBE4B deficiency leads to CCAR2 accumulation, which inhibits SIRT1 activity, thereby increasing p53 acetylation and stability and promoting apoptosis. UBE4B also directly targets p53 for degradation (dominant pathway), revealed by rescue experiments. Orthogonal ubiquitin transfer (OUT) screen, co-immunoprecipitation, ubiquitination assay, SIRT1 activity assay, p53 acetylation western blot, transcriptional profiling, rescue experiments International journal of molecular sciences Medium 42074320
2026 CCAR2 binds ERα and alters its nuclear translocation, increasing apoptotic transcriptional activity in osteoclasts, thereby reducing osteoclast numbers. CCAR2 knockout RAW264.7 cells generated by CRISPR-Cas9 show increased osteoclast formation, reduced ROS, and decreased apoptosis during osteoclastogenesis. CRISPR-Cas9 CCAR2 knockout, osteoclast differentiation assay (RANKL/M-CSF), co-immunoprecipitation (CCAR2–ERα), nuclear translocation assay, apoptosis assay, ROS measurement Acta biochimica et biophysica Sinica Medium 42212624
2026 Genistein directly binds CCAR2 (binding site identified at Trp108) and disrupts the CCAR2–SIRT1 inhibitory interaction, restoring SIRT1 deacetylase activity; this reduces p53 acetylation and p53-driven pro-fibrotic signaling. Liver-specific Ccar2 deletion recapitulates the hepatoprotective effect, confirming CCAR2 as a direct pharmacological target. Biotin-conjugated genistein pull-down + mass spectrometry, CETSA, molecular docking, Co-immunoprecipitation, SIRT1 activity assay, p53 acetylation assay, liver-specific Ccar2 KO mouse model Phytomedicine Medium 41775214
2026 Ginsenoside Rf directly binds CCAR2 and disrupts the CCAR2–SIRT1 interaction, releasing SIRT1 to deacetylate FXR; this promotes FXR nuclear translocation and transcriptional activation of bile acid metabolism genes, protecting against acetaminophen-induced liver injury. Liver-specific Ccar2 deletion attenuates APAP injury and abolishes the ginsenoside Rf hepatoprotective effect. Pull-down assay (ginsenoside Rf as bait), RNA sequencing, Co-immunoprecipitation (CCAR2–SIRT1), FXR acetylation and nuclear translocation assay, liver-specific Ccar2 KO mice, AILI mouse model British journal of pharmacology Medium 41825964

Source papers

Stage 0 corpus · 37 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2007 Modulation of estrogen receptor alpha protein level and survival function by DBC-1. Molecular endocrinology (Baltimore, Md.) 65 17473282
2021 Hydrogen sulfide-induced GAPDH sulfhydration disrupts the CCAR2-SIRT1 interaction to initiate autophagy. Autophagy 53 33459133
2016 A genome-wide screening uncovers the role of CCAR2 as an antagonist of DNA end resection. Nature communications 41 27503537
2013 Deleted in breast cancer-1 (DBC-1) in the interface between metabolism, aging and cancer. Bioscience reports 39 23841676
2015 DBC1/CCAR2 is involved in the stabilization of androgen receptor and the progression of osteosarcoma. Scientific reports 38 26249023
2019 CCAR2/DBC1 and Hsp60 Positively Regulate Expression of Survivin in Neuroblastoma Cells. International journal of molecular sciences 31 30609639
2019 Acetylation of CCAR2 Establishes a BET/BRD9 Acetyl Switch in Response to Combined Deacetylase and Bromodomain Inhibition. Cancer research 31 30643017
2020 CCAR1 and CCAR2 as gene chameleons with antagonistic duality: Preclinical, human translational, and mechanistic basis. Cancer science 25 33403784
2014 DBC1/CCAR2 and CCAR1 Are Largely Disordered Proteins that Have Evolved from One Common Ancestor. BioMed research international 24 25610865
2016 A novel crosstalk between CCAR2 and AKT pathway in the regulation of cancer cell proliferation. Cell death & disease 23 27809307
2015 CCAR2/DBC1 is required for Chk2-dependent KAP1 phosphorylation and repair of DNA damage. Oncotarget 23 26158765
2013 hMOF acetylation of DBC1/CCAR2 prevents binding and inhibition of SirT1. Molecular and cellular biology 23 24126058
2016 CCAR2 Is Required for Proliferation and Tumor Maintenance in Human Squamous Cell Carcinoma. The Journal of investigative dermatology 22 27725203
2023 Mechanistic insights into the dual role of CCAR2/DBC1 in cancer. Experimental & molecular medicine 21 37524873
2014 CCAR2 deficiency augments genotoxic stress-induced apoptosis in the presence of melatonin in non-small cell lung cancer cells. Tumour biology : the journal of the International Society for Oncodevelopmental Biology and Medicine 21 25085583
2015 High DBC1 (CCAR2) expression in gallbladder carcinoma is associated with favorable clinicopathological factors. International journal of clinical and experimental pathology 13 26617872
2022 CCAR2 functions downstream of the Shieldin complex to promote double-strand break end-joining. Proceedings of the National Academy of Sciences of the United States of America 12 36442094
2015 CCAR2 negatively regulates nuclear receptor LXRα by competing with SIRT1 deacetylase. The Journal of steroid biochemistry and molecular biology 12 25661920
2017 Mitochondrial CCAR2/DBC1 is required for cell survival against rotenone-induced mitochondrial stress. Biochemical and biophysical research communications 11 28254432
2022 MiR-342-5p protects neurons from cerebral ischemia induced-apoptosis through regulation of Akt/NF-κB pathways by targeting CCAR2. Journal of stroke and cerebrovascular diseases : the official journal of National Stroke Association 8 36434857
2021 Chromatin remodeling factor CECR2 forms tissue-specific complexes with CCAR2 and LUZP1. Biochemistry and cell biology = Biochimie et biologie cellulaire 8 34197713
2021 CCAR2 promotes a malignant phenotype of osteosarcoma through Wnt/β-catenin-dependent transcriptional activation of SPARC. Biochemical and biophysical research communications 7 34624572
2017 CCAR2 negatively regulates IL-8 production in cervical cancer cells. Oncotarget 7 29416683
2024 CircMETTL9 targets CCAR2 to induce neuronal oxidative stress and apoptosis via mitochondria-mediated pathways following traumatic brain injury. Free radical biology & medicine 5 39709098
2022 CCAR2 controls mitotic progression through spatiotemporal regulation of Aurora B. Cell death & disease 5 35672287
2022 Role of lncRNA MIAT/miR-361-3p/CCAR2 in prostate cancer cells. Open medicine (Warsaw, Poland) 5 36245704
2024 CircKRT75 augments the cisplatin chemoresistance of nasopharyngeal carcinoma via targeting miR-659/CCAR2 axis. Journal of molecular histology 4 39612069
2025 Tissue Factor Pathway Inhibitor 2 Enhances Hepatocellular Carcinoma Chemosensitivity by Activating CCAR2-GADD45A-Mediated DNA Damage Repair. International journal of biological sciences 3 40765823
2025 Kaempferol Alleviates Dry Eye Disease Via Modulation of the IDH3B/CCAR2/IKBKB Axis. Investigative ophthalmology & visual science 3 40980968
2023 The effect of 24-hour sleep deprivation and anaerobic exercise on the expression of BAX, BCL2, BMAL1 and CCAR2 genes in peripheral blood mononuclear cells after L-arginine supplementation. Gene 2 37625565
2025 ASFV p30 interacts with CCAR2 and MATR3 to promote ASFV replication. Veterinary microbiology 1 39919500
2025 LNCAROD was stabilized through N6-methyladenosine methylation and exerted its anticancer effects in lung squamous cell carcinoma by inhibiting SIRT1 activity via CCAR2. Translational lung cancer research 1 40386722
2026 Genistein suppresses renal fibrosis in chronic kidney disease through regulation of the CCAR2/SIRT1/p53 signaling axis. Phytomedicine : international journal of phytotherapy and phytopharmacology 0 41775214
2026 Ginsenoside Rf protects against acetaminophen-induced liver injury by targeting CCAR2 to activate the SIRT1-FXR signalling pathway. British journal of pharmacology 0 41825964
2026 Dual Pathways of UBE4B Inhibit Apoptosis in p53-Positive Tumor Cells via CCAR2 Degradation. International journal of molecular sciences 0 42074320
2026 CCAR2 reduces the number of osteoclasts by controlling osteoclast apoptosis. Acta biochimica et biophysica Sinica 0 42212624
2025 CCAR2 Drives Glioma Cell Survival by Positively Regulating SIRT1 and Activating the Notch1/c-Myc Pathway. Drug development research 0 40986003

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