Affinage

ERCC8

DNA excision repair protein ERCC-8 · UniProt Q13216

Length
396 aa
Mass
44.1 kDa
Annotated
2026-04-28
100 papers in source corpus 16 papers cited in narrative 15 extracted findings

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

ERCC8 (CSA) is a WD40-repeat protein that functions as the substrate-recognition subunit of the CRL4^CSA E3 ubiquitin ligase complex, serving as a central organizer of transcription-coupled nucleotide excision repair (TC-NER) and transcription-coupled DNA-protein crosslink repair. Following UV-induced transcription arrest, CSA translocates to the nuclear matrix in a CSB- and TFIIH-dependent manner, where it ubiquitinates CSB to promote its proteasomal degradation—a step required for post-repair transcription recovery—and recruits UVSSA/KIAA1530 to coordinate downstream repair (PMID:12732143, PMID:16751180, PMID:17242193, PMID:22902626). Loss of CSA specifically abolishes repair of cyclobutane pyrimidine dimers from the transcribed strand of active genes while leaving global genome repair intact, and CSA-deficient cells also fail to resolve transcription-blocking DNA-protein crosslinks through a pathway independent of UVSSA and XPA (PMID:12509261, PMID:38600235). Biallelic loss-of-function mutations in ERCC8 cause Cockayne syndrome complementation group A, a disorder characterized by UV sensitivity and defective TC-NER (PMID:8596535, PMID:19525295).

Mechanistic history

Synthesis pass · year-by-year structured walk · 10 steps
  1. 1996 Medium

    Genetic complementation established that ERCC8 is identical to the Cockayne syndrome group A (CS-A) gene and that its protein product is specifically required for transcription-coupled repair of cyclobutane pyrimidine dimers but not (6-4) photoproducts, defining CSA as a TC-NER-specific factor.

    Evidence Cell fusion and transfection complementation of rodent group 8 mutants, immunoslot-blot UV photoproduct quantification; yeast RAD28 null mutant UV sensitivity and strand-specific repair analysis

    PMID:8596535 PMID:8830695

    Open questions at the time
    • Biochemical function of the CSA protein was unknown
    • Why yeast ortholog RAD28 deletion has no phenotype remained unexplained
    • Protein partners and enzymatic activity of CSA were uncharacterized
  2. 2002 High

    A Csa-knockout mouse model confirmed that CSA is essential for TC-NER in vivo—knockout MEFs failed to remove CPDs from the transcribed strand and could not resume RNA synthesis after UV—while global genome repair was unaffected, cementing the TC-NER-specific requirement.

    Evidence CSA-null mouse embryonic fibroblasts analyzed by UV survival, unscheduled DNA synthesis, RNA synthesis recovery, and strand-specific repair

    PMID:12509261

    Open questions at the time
    • Molecular mechanism by which CSA promotes TC-NER was still undefined
    • Whether CSA had enzymatic activity or served as an adaptor was unknown
  3. 2003 High

    Identification of CSA as a subunit of a DDB1–cullin 4A–Roc1 E3 ubiquitin ligase complex revealed that CSA functions as an enzymatic scaffold rather than a passive adaptor, and that the COP9 signalosome regulates its ligase activity upon UV irradiation.

    Evidence Co-immunoprecipitation, biochemical fractionation, in vitro ubiquitin ligase assay, and RNAi knockdown in human cells

    PMID:12732143

    Open questions at the time
    • The physiological substrate(s) of the CRL4^CSA ubiquitin ligase were unknown
    • Whether CSA ubiquitin ligase activity was required for TC-NER completion was untested
  4. 2006 High

    CSB was identified as a direct substrate of the CSA-containing E3 ligase: CSA mediates UV-dependent proteasomal degradation of CSB, and this degradation is required for post-TC-NER transcription recovery, establishing a feedback loop within TC-NER.

    Evidence Ubiquitination assays, proteasome inhibitor treatment, CSA-deficient cell complementation, and transcription recovery measurement

    PMID:16751180

    Open questions at the time
    • Temporal regulation of CSB ubiquitination relative to repair intermediate processing was unclear
    • Additional substrates of the CRL4^CSA ligase were not identified
  5. 2007 High

    CSA was shown to translocate to the nuclear matrix after UV irradiation and co-localize with hyperphosphorylated RNA Pol II, and this recruitment depends on CSB, functional TFIIH, and active transcription elongation, placing CSA action downstream of lesion-stalled Pol II.

    Evidence Cell fractionation, immunofluorescence, cell-free reconstitution, and complementation with TCR-defective CSA mutants

    PMID:17242193

    Open questions at the time
    • How CSA recognizes the stalled Pol II complex structurally was undetermined
    • Whether CSA translocation requires direct protein-protein contact with CSB or TFIIH was not resolved
  6. 2012 High

    CSA was found to recruit UVSSA/KIAA1530 to UV-damaged chromatin, and a patient-derived CSA-W361C mutation disrupted this interaction, identifying UVSSA recruitment as a critical downstream effector function of CSA in TC-NER.

    Evidence Co-immunoprecipitation, chromatin fractionation, siRNA knockdown, UV sensitivity assays, and patient mutation analysis

    PMID:22902626

    Open questions at the time
    • Whether UVSSA recruitment and CSB degradation are sequential or parallel outputs of CSA was not clarified
    • Structural basis of the CSA–UVSSA interface was unknown
  7. 2011 Medium

    CSA was found to associate with p53 and Mdm2, stimulating Mdm2-dependent p53 ubiquitination, extending the function of the CRL4^CSA complex beyond TC-NER into stress-responsive p53 regulation.

    Evidence Tandem affinity purification, mass spectrometry, co-immunoprecipitation, and in vitro ubiquitination assay

    PMID:22032989

    Open questions at the time
    • Whether p53 ubiquitination by this complex occurs physiologically during TC-NER or in a separate context was unclear
    • Independent replication of this finding is lacking
    • In vivo consequences for p53 stability and cell fate were not demonstrated
  8. 2018 Medium

    CSA was shown to participate in repair of MMS-induced single- and double-strand breaks and to suppress NHEJ in S/G2 phase, indicating CSA functions extend to replication-associated damage beyond canonical UV-induced TC-NER.

    Evidence γH2AX analysis by cell cycle phase, comet assay, and MMS/IR treatment of CS-A primary and transformed cells

    PMID:29545921

    Open questions at the time
    • The mechanism by which CSA suppresses NHEJ in S/G2 was not defined
    • Whether this function requires the CRL4^CSA ubiquitin ligase activity was untested
  9. 2020 Medium

    CSA depletion was linked to mitochondrial dysfunction including impaired dynamics and mitophagy, rescuable by NAD+ precursor supplementation, implicating CSA in mitochondrial homeostasis through NAD+ signaling.

    Evidence Cross-species transcriptomics (CS patient brain, mouse, C. elegans), siRNA depletion in primary cells, NAD+ supplementation rescue, lifespan assays

    PMID:33166073

    Open questions at the time
    • Whether CSA acts directly in mitochondria or indirectly via nuclear signaling was unresolved
    • The molecular target of CSA in NAD+ metabolism was not identified
  10. 2024 High

    Two independent studies demonstrated that CSA and the CRL4^CSA ligase are required for transcription-coupled repair of DNA-protein crosslinks, a pathway that involves Pol II ubiquitylation and degradation but is independent of downstream TC-NER factors UVSSA and XPA, revealing a mechanistically distinct arm of CSA function.

    Evidence Genome-wide DPC-seq, RNA synthesis recovery, genetic epistasis in CSA/CSB/UVSSA/XPA knockouts, ubiquitylation assays

    PMID:38600235 PMID:38600236

    Open questions at the time
    • How CRL4^CSA distinguishes DPC-stalled from CPD-stalled Pol II to channel into different downstream pathways is unknown
    • Whether DPC repair by CSA requires the same COP9 signalosome regulation as UV-induced TC-NER is untested

Open questions

Synthesis pass · forward-looking unresolved questions
  • A high-resolution structure of the CRL4^CSA complex engaged with stalled Pol II and its substrates (CSB, Pol II at DPCs) is lacking, leaving the structural basis of substrate discrimination and the coordination between CSA's multiple repair outputs unresolved.
  • No cryo-EM or crystal structure of CRL4^CSA bound to Pol II or CSB
  • Mechanism of COP9 signalosome-mediated regulation of CSA ligase activity after UV is incompletely defined
  • How CSA promotes mitochondrial homeostasis at the molecular level is unknown

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0140096 catalytic activity, acting on a protein 3 GO:0060090 molecular adaptor activity 2
Localization
GO:0005634 nucleus 2 GO:0005694 chromosome 2
Pathway
R-HSA-73894 DNA Repair 8 R-HSA-392499 Metabolism of proteins 3 R-HSA-74160 Gene expression (Transcription) 3
Partners
CUL4ADDB1ERCC6GTF2H1MDM2RBX1TP53UVSSA
Complex memberships
CRL4^CSA (DDB1-CUL4A-RBX1-CSA)

Evidence

Reading pass · 15 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2003 CSA (ERCC8) is integrated into an E3 ubiquitin ligase complex containing DDB1, cullin 4A, and Roc1, and this complex displays ubiquitin ligase activity. The COP9 signalosome (CSN) differentially regulates the ubiquitin ligase activity of the CSA complex in response to UV irradiation. Co-immunoprecipitation, biochemical fractionation, in vitro ubiquitin ligase assay, RNA interference knockdown Cell High 12732143
2006 CSA (ERCC8) mediates proteasome-dependent degradation of CSB following UV irradiation; CSB is a substrate of the CSA-containing E3 ubiquitin ligase. This degradation of CSB is required for post-TCR recovery of transcription. Ubiquitination assay, proteasome inhibitor treatment, CSA-deficient cell complementation, transcription recovery assay Genes & development High 16751180
2007 CSA protein is translocated to the nuclear matrix after UV irradiation, where it co-localizes with hyperphosphorylated RNA polymerase II. This translocation is dependent on CSB, functional TFIIH, chromatin structure, and transcription elongation. Cell fractionation, immunofluorescence, cell-free reconstitution system, UV irradiation, complementation with TCR-defective CSA mutants Molecular and cellular biology High 17242193
2012 CSA (ERCC8) recruits KIAA1530 (UVSSA) onto chromatin after UV irradiation in a CSA-dependent manner. KIAA1530 interacts with CSA and TFIIH and is required for TCR; KIAA1530 depletion destabilizes CSB after UV. A patient-derived CSA mutant (W361C) fails to bind KIAA1530, establishing a direct mechanistic link. Co-immunoprecipitation, chromatin fractionation, UV sensitivity assay, siRNA knockdown, patient mutation analysis The Journal of biological chemistry High 22902626
2011 CSA and CSB proteins associate in a complex with p53 and Mdm2; this interaction stimulates Mdm2-dependent ubiquitination of p53. CSA and CSB function within a Cullin Ring Ubiquitin Ligase complex responsible for p53 ubiquitination under cellular stress. Tandem affinity purification, co-immunoprecipitation, mass spectrometry, ubiquitination assay Cell cycle (Georgetown, Tex.) Medium 22032989
2007 CSA protein contributes in vivo to repair of oxidatively induced DNA lesions (8-hydroxyguanine and 8,5'-cyclo-2'-deoxyadenosine). Expression of wild-type CSA in CS-A cells decreased steady-state 8-OH-Gua levels and increased repair rate; however, CS-A cell extracts showed normal 8-OH-Gua cleavage activity in vitro, indicating CSA acts upstream of base excision repair in an accessory capacity. Cell complementation with wild-type CSA, oxidative lesion quantification by HPLC-MS/MS, in vitro incision assay with cell extracts, UV and oxidant treatment Oncogene Medium 17297471
1996 The yeast RAD28 gene is the Saccharomyces cerevisiae homolog of human CSA/ERCC8. A rad28 null mutant does not show increased sensitivity to UV or other DNA-damaging agents and does not display defects in strand-specific repair of the RPB2 gene, indicating RAD28/CSA has a distinct or redundant role in yeast TCR compared to its human counterpart. Gene disruption, UV sensitivity assay, strand-specific repair analysis by Southern blot, complementation testing Journal of bacteriology Medium 8830695
1996 Rodent complementation group 8 (ERCC8) corresponds to Cockayne syndrome complementation group A. The group 8 mutant cell line shows failure to repair cyclobutane pyrimidine dimers from active genes (TCR defect) while (6-4) photoproducts are repaired normally, confirming the TCR-specific role of ERCC8/CSA. Cell fusion complementation, transfection complementation, immunoslot-blot quantification of UV photoproducts over time Mutation research Medium 8596535
2002 CSA-deficient (Csa-/-) mouse embryonic fibroblasts are UV-sensitive, show normal global genome repair (unscheduled DNA synthesis intact), fail to resume RNA synthesis after UV exposure, and cannot remove cyclobutane pyrimidine dimers from the transcribed strand of active genes, establishing CSA as specifically required for transcription-coupled NER in vivo. Mouse knockout model, UV survival assay, unscheduled DNA synthesis, RNA synthesis recovery assay, strand-specific repair analysis DNA repair High 12509261
2024 CSA and CSB are required for transcription-coupled repair of DNA-protein crosslinks (DPCs). DPC formation arrests transcription and induces ubiquitylation and degradation of RNA polymerase II. CSA-deficient cells fail to efficiently restart transcription after DPC induction. The CRL4CSA ubiquitin ligase and the proteasome mediate TC-DPC repair, acting independently of SPRTN and downstream TC-NER factors (UVSSA, XPA are dispensable). Genetic screens, DPC sequencing (genome-wide mapping), RNA synthesis recovery assay, genetic epistasis (CSA/CSB/UVSSA/XPA knockouts), ubiquitylation assays Nature cell biology High 38600235 38600236
2013 The CSA protein contains seven WD40 repeat motifs arranged in a beta-propeller architecture. This structural framework supports its role as a substrate-recognition subunit of the CRL4CSA E3 ubiquitin ligase complex in TC-NER. Structural analysis (WD40 domain prediction), functional review integrating biochemical data Mechanisms of ageing and development Low 23571135
2020 CSA and CSB proteins are required for mitochondrial homeostasis. Depletion of CSA or CSB in primary cells leads to mitochondrial dysfunction (impaired dynamics and mitophagy) that can be corrected by NAD+ precursor supplementation, linking nuclear TC-NER proteins to mitochondrial integrity. Transcriptomic analysis of CS patient brain tissue and mouse/nematode models, siRNA depletion of CSA/CSB in primary cells, NAD+ supplementation rescue experiments, lifespan assays in C. elegans Aging cell Medium 33166073
2004 In contrast to CSB-deficient mouse embryonic fibroblasts, CSA-deficient MEFs are not hypersensitive to gamma-ray or paraquat-induced oxidative damage, revealing that CSA and CSB perform separate roles in DNA damage response pathways: CSA is not required for repair of oxidative lesions at the cellular level in fibroblasts. Mouse knockout MEFs and keratinocytes, gamma-ray and paraquat sensitivity assays, in vivo dietary oxidative stress model Molecular and cellular biology Medium 15340056
2009 ERCC8 (CSA) is located on chromosome 5 in a contiguous gene region with NDUFAF2 and ELOVL7. Homozygous deletion of ERCC8 results in defective transcription-coupled NER, establishing the necessity of ERCC8 protein for TC-NER in human cells, confirmed by baculoviral complementation restoring TC-NER function. Homozygous deletion patient cells, TC-NER assay (RNA synthesis recovery), baculoviral complementation Human molecular genetics Medium 19525295
2018 CSA and CSB proteins play a role in the repair of single-strand and double-strand DNA breaks. Following MMS treatment, CS-A cells accumulate unrepaired single-strand breaks leading to double-strand breaks in S and G2 phases; CSA suppresses NHEJ in S and G2 phase, with distinct repair kinetics compared to CSB, suggesting the two proteins act at different times in DNA break repair. γH2AX phosphorylation analysis by cell cycle phase, comet assay, MMS and ionizing radiation treatment of CS-A and CS-B primary and transformed cells Oncotarget Medium 29545921

Source papers

Stage 0 corpus · 100 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
1992 FK-506- and CsA-sensitive activation of the interleukin-2 promoter by calcineurin. Nature 846 1377361
2000 Two multicenter, randomized studies of the efficacy and safety of cyclosporine ophthalmic emulsion in moderate to severe dry eye disease. CsA Phase 3 Study Group. Ophthalmology 677 10768324
2003 The ubiquitin ligase activity in the DDB2 and CSA complexes is differentially regulated by the COP9 signalosome in response to DNA damage. Cell 600 12732143
1991 Two cytoplasmic candidates for immunophilin action are revealed by affinity for a new cyclophilin: one in the presence and one in the absence of CsA. Cell 388 1652374
2006 CSA-dependent degradation of CSB by the ubiquitin-proteasome pathway establishes a link between complementation factors of the Cockayne syndrome. Genes & development 213 16751180
2010 Mutation update for the CSB/ERCC6 and CSA/ERCC8 genes involved in Cockayne syndrome. Human mutation 187 19894250
1985 The effect of interleukin 3 and GM-CSA-2 on megakaryocyte and myeloid clonal colony formation. Blood 162 3917313
2005 Identification of multiple chondroitin sulfate A (CSA)-binding domains in the var2CSA gene transcribed in CSA-binding parasites. The Journal of infectious diseases 129 15717280
2010 Full-length extracellular region of the var2CSA variant of PfEMP1 is required for specific, high-affinity binding to CSA. Proceedings of the National Academy of Sciences of the United States of America 126 20194779
2007 The role of CSA in the response to oxidative DNA damage in human cells. Oncogene 120 17297471
1979 Granulocytosis and colony-stimulating activity (CSA) produced by a human squamous cell carcinoma. Cancer 103 311241
2018 The C-S-A gene system regulates hull pigmentation and reveals evolution of anthocyanin biosynthesis pathway in rice. Journal of experimental botany 96 29361187
2004 Different effects of CSA and CSB deficiency on sensitivity to oxidative DNA damage. Molecular and cellular biology 89 15340056
2009 Novel inhibitors of the calcineurin/NFATc hub - alternatives to CsA and FK506? Cell communication and signaling : CCS 86 19860902
2002 UVB radiation-induced cancer predisposition in Cockayne syndrome group A (Csa) mutant mice. DNA repair 85 12509261
1992 Overexpression of the csA cell adhesion molecule under its own cAMP-regulated promoter impairs morphogenesis in Dictyostelium. Journal of cell science 82 1328260
1997 Effects of the immunosuppressive drugs CsA and FK506 on intracellular signalling and gene regulation. Immunobiology 70 9442391
1989 Biochemical characterization of the inhibitory effect of CsA on cytolytic T lymphocyte effector functions. Journal of immunology (Baltimore, Md. : 1950) 69 2541201
2012 KIAA1530 protein is recruited by Cockayne syndrome complementation group protein A (CSA) to participate in transcription-coupled repair (TCR). The Journal of biological chemistry 56 22902626
1993 Calcineurin-dependent growth of an FK506- and CsA-hypersensitive mutant of Saccharomyces cerevisiae. Journal of general microbiology 54 7510323
2006 Resveratrol prevents CsA inhibition of proliferation and osteoblastic differentiation of mouse bone marrow-derived mesenchymal stem cells through an ER/NO/cGMP pathway. Toxicology in vitro : an international journal published in association with BIBRA 53 16524694
2006 Insight into the CSA tensors of nucleobase carbons in RNA polynucleotides from solution measurements of residual CSA: towards new long-range orientational constraints. Journal of magnetic resonance (San Diego, Calif. : 1997) 52 16431143
1998 Detection of subtle phenotypes: the case of the cell adhesion molecule csA in Dictyostelium. Proceedings of the National Academy of Sciences of the United States of America 52 9689085
2005 Weak alignment of paramagnetic proteins warrants correction for residual CSA effects in measurements of pseudocontact shifts. Journal of the American Chemical Society 50 16332059
1986 The effects of cyclosporin A (CsA) on hepatic microsomal drug metabolism in the rat. Drug metabolism and disposition: the biological fate of chemicals 50 2868869
2011 CSA and CSB proteins interact with p53 and regulate its Mdm2-dependent ubiquitination. Cell cycle (Georgetown, Tex.) 49 22032989
2015 Bactericidal Activity of Ceragenin CSA-13 in Cell Culture and in an Animal Model of Peritoneal Infection. Antimicrobial agents and chemotherapy 48 26248361
1996 Molecular cloning and characterization of Saccharomyces cerevisiae RAD28, the yeast homolog of the human Cockayne syndrome A (CSA) gene. Journal of bacteriology 46 8830695
2024 Transcription-coupled repair of DNA-protein cross-links depends on CSA and CSB. Nature cell biology 45 38600235
2005 Provinol prevents CsA-induced nephrotoxicity by reducing reactive oxygen species, iNOS, and NF-kB expression. The journal of histochemistry and cytochemistry : official journal of the Histochemistry Society 45 15956028
2009 Bactericidal activities of the cationic steroid CSA-13 and the cathelicidin peptide LL-37 against Helicobacter pylori in simulated gastric juice. BMC microbiology 44 19728885
2016 Microarray and genetic analysis reveals that csa-miR159b plays a critical role in abscisic acid-mediated heat tolerance in grafted cucumber plants. Plant, cell & environment 42 27037862
2018 CsA attenuates compression-induced nucleus pulposus mesenchymal stem cells apoptosis via alleviating mitochondrial dysfunction and oxidative stress. Life sciences 41 29746847
2024 Transcription-coupled DNA-protein crosslink repair by CSB and CRL4CSA-mediated degradation. Nature cell biology 40 38600236
2020 Cockayne syndrome proteins CSA and CSB maintain mitochondrial homeostasis through NAD+ signaling. Aging cell 40 33166073
2013 The role of Cockayne syndrome group A (CSA) protein in transcription-coupled nucleotide excision repair. Mechanisms of ageing and development 40 23571135
2009 Chondroitin sulphate A (CSA)-binding of single recombinant Duffy-binding-like domains is not restricted to Plasmodium falciparum Erythrocyte Membrane Protein 1 expressed by CSA-binding parasites. International journal for parasitology 40 19324047
2013 The role of CSA and CSB protein in the oxidative stress response. Mechanisms of ageing and development 38 23562424
2021 Cardiac Surgery Associated AKI Prevention Strategies and Medical Treatment for CSA-AKI. Journal of clinical medicine 37 34830567
2008 Var2CSA DBL6-epsilon domain expressed in HEK293 induces limited cross-reactive and blocking antibodies to CSA binding parasites. Malaria journal 36 18771584
1975 Identification of a colon-specific antigen (CSA) in normal and neoplastic tissues. Journal of immunology (Baltimore, Md. : 1950) 36 46258
2018 Targeted delivery of doxorubicin by CSA-binding nanoparticles for choriocarcinoma treatment. Drug delivery 35 29426237
2016 Klotho mitigates cyclosporine A (CsA)-induced epithelial-mesenchymal transition (EMT) and renal fibrosis in rats. International urology and nephrology 35 27796696
2001 Apoptotic cell death of cultured salamander photoreceptors induced by cccp: CsA-insensitive mitochondrial permeability transition. Journal of cell science 35 11309197
2009 Contiguous gene deletion of ELOVL7, ERCC8 and NDUFAF2 in a patient with a fatal multisystem disorder. Human molecular genetics 31 19525295
2013 Cajaninstilbene acid (CSA) exerts cytoprotective effects against oxidative stress through the Nrf2-dependent antioxidant pathway. Toxicology letters 30 23535287
2008 CsA can induce DNA double-strand breaks: implications for BMT regimens particularly for individuals with defective DNA repair. Bone marrow transplantation 30 18278071
2004 Disruption of mitochondrial membrane potential during apoptosis induced by PSC 833 and CsA in multidrug-resistant lymphoid leukemia. Toxicology and applied pharmacology 29 15289089
2001 Adjunctive rapamycin and CsA treatment inhibits monocyte/macrophage associated cytokines/chemokines in sensitized cardiac graft recipients. Transplantation 29 11374423
2017 Comparative pharmacokinetic profile of cyclosporine (CsA) with a decapeptide and a linear analogue. Organic & biomolecular chemistry 27 28266673
1989 Carbohydrate components recognized by the cone-specific monoclonal antibody CSA-1 and by peanut agglutinin are associated with red and green-sensitive cone photoreceptors. The Journal of comparative neurology 25 2808775
1979 Factors promoting colony stimulating activity (CSA) production in macrophages and epithelial cells. Experimental hematology 25 225188
2007 Functional TFIIH is required for UV-induced translocation of CSA to the nuclear matrix. Molecular and cellular biology 24 17242193
2003 Lack of role for CsA-sensitive or Fas pathways in the tolerization of CD4 T cells via BMT and anti-CD40L. American journal of transplantation : official journal of the American Society of Transplantation and the American Society of Transplant Surgeons 24 12814472
1998 CsA-sensitive purine-box transcriptional regulator in bronchial epithelial cells contains NF45, NF90, and Ku. The American journal of physiology 24 9843854
2015 Parity-dependent recognition of DBL1X-3X suggests an important role of the VAR2CSA high-affinity CSA-binding region in the development of the humoral response against placental malaria. Infection and immunity 23 25824842
2003 CKN1 (MIM 216400): mutations in Cockayne syndrome type A and a new common polymorphism. Journal of human genetics 23 14661080
2018 Purification, characterization of Chondroitinase ABC from Sphingomonas paucimobilis and in vitro cardiocytoprotection of the enzymatically degraded CS-A. International journal of biological macromolecules 22 29702169
2009 CSA: an efficient algorithm to improve circular DNA multiple alignment. BMC bioinformatics 22 19627599
2007 Sanglifehrin a blocks key dendritic cell functions in vivo and promotes long-term allograft survival together with low-dose CsA. American journal of transplantation : official journal of the American Society of Transplantation and the American Society of Transplant Surgeons 22 17391124
1996 Susceptibility to clinically manifest cyclosporine A (CsA)-induced autoimmune disease is associated with interferon-gamma (IFN-gamma)-producing CD45RC+RT6- T helper cells. Clinical and experimental immunology 22 8809139
1995 Accessory signalling by B7-1 for T cell activation induced by anti-CD2: evidence for IL-2-independent CTL generation and CsA-resistant cytokine production. Scandinavian journal of immunology 22 7529939
1982 In vitro effects of cyclosporin A (CSA) on human hemopoietic cell lines. Immunopharmacology 22 6819253
1979 Properties and separation of T lymphocyte growth stimulatory activity (TL-GSA) and of granulocyte-macrophage colony stimulatory activity (GM-CSA) produced separately from two human T lymphocyte subpopulations. Journal of cellular physiology 22 315950
2021 Bactericidal Properties of Rod-, Peanut-, and Star-Shaped Gold Nanoparticles Coated with Ceragenin CSA-131 against Multidrug-Resistant Bacterial Strains. Pharmaceutics 21 33809901
2018 CSA and CSB play a role in the response to DNA breaks. Oncotarget 21 29545921
2015 Local delivery of the cationic steroid antibiotic CSA-90 enables osseous union in a rat open fracture model of Staphylococcus aureus infection. The Journal of bone and joint surgery. American volume 21 25695982
2013 Mitochondrial CSA and CSB: protein interactions and protection from ageing associated DNA mutations. Mechanisms of ageing and development 21 23562423
2004 Estimates of methyl 13C and 1H CSA values (Deltasigma) in proteins from cross-correlated spin relaxation. Journal of biomolecular NMR 21 15630560
2003 Multidrug resistance modulators PSC 833 and CsA show differential capacity to induce apoptosis in lymphoid leukemia cell lines independently of their MDR phenotype. Leukemia research 21 12620293
1988 Frequency of human alloantigen-reactive T lymphocytes. III. Evidence that cyclosporine has an inhibitory effect on human CTL and CTL precursors, independent of CsA-mediated helper T cell dysfunction. Transplantation 20 2970141
1988 Abnormal distribution of T cell subsets in the thymus of cyclosporin A (CsA)-treated mice. Thymus 20 3262940
2016 Mutations in Cockayne Syndrome-Associated Genes (Csa and Csb) Predispose to Cisplatin-Induced Hearing Loss in Mice. The Journal of neuroscience : the official journal of the Society for Neuroscience 19 27122034
2006 Inhibition of calcineurin by infusion of CsA causes hyperphosphorylation of tau and is accompanied by abnormal behavior in mice. Biological chemistry 19 16913847
2023 Cyclosporine A (CsA) prevents synaptic impairment caused by truncated tau by caspase-3. Molecular and cellular neurosciences 18 37182572
2021 Tanshinone IIA combined with CsA inhibit myocardial cell apoptosis induced by renal ischemia-reperfusion injury in obese rats. BMC complementary medicine and therapies 18 33752661
2018 Ceragenin CSA-13 as free molecules and attached to magnetic nanoparticle surfaces induce caspase-dependent apoptosis in human breast cancer cells via disruption of cell oxidative balance. Oncotarget 17 29774111
2014 Requirement of miR-144 in CsA induced proliferation and invasion of human trophoblast cells by targeting titin. Journal of cellular biochemistry 17 24453045
2009 Pharmacokinetics of CsA during the switch from continuous intravenous infusion to oral administration after allogeneic hematopoietic stem cell transplantation. Bone marrow transplantation 17 19898510
2003 Simvastatin-induced rhabdomyolysis in a CsA-treated renal transplant recipient. Medical science monitor : international medical journal of experimental and clinical research 17 12960932
2000 A combination of cyclosporin-A (CsA) and interferon-gamma (INF-gamma) induces apoptosis in human gastric carcinoma cells. Anticancer research 17 11131636
1996 Rodent complementation group 8 (ERCC8) corresponds to Cockayne syndrome complementation group A. Mutation research 17 8596535
2019 Phosphorylation of the VAR2CSA extracellular region is associated with enhanced adhesive properties to the placental receptor CSA. PLoS biology 16 31181082
2000 Comparative sequence analysis (CSA): a new sequence-based method for the identification and characterization of mutations in DNA. Human mutation 16 11058902
2005 Protein structure prediction with the UNRES force-field using Replica-Exchange Monte Carlo-with-Minimization; Comparison with MCM, CSA, and CFMC. Journal of computational chemistry 15 16088925
1995 Cyclosporin A (CsA) modulates the glomerular production of inflammatory mediators and proteoglycans in experimental nephrosis. Clinical and experimental immunology 15 8536380
1994 Partial characterization of a 52 kDa CsA/FK506/rapamycin binding protein. Clinical biochemistry 15 7532557
1992 Correlation between up-regulation of lymphokine mRNA and down-regulation of TcR, CD4, CD8 and lck mRNA as shown by the effect of CsA on activated T lymphocytes. Biochemical and biophysical research communications 15 1497650
1985 Effect of cyclosporin-A (CsA) on the ability of T lymphocyte subsets to inhibit the proliferation of autologous EBV-transformed B cells. International journal of cancer 15 2982748
2021 Prediction of cardiac surgery associated - acute kidney injury (CSA-AKI) by healthcare professionals and urine cell cycle arrest AKI biomarkers [TIMP-2]*[IGFBP7]: A single center prospective study (the PREDICTAKI trial). Journal of critical care 14 34741963
2001 Human alloantigen-specific anergic cells induced by a combination of CTLA4-Ig and CsA maintain anti-leukemia and anti-viral cytotoxic responses. Bone marrow transplantation 14 11548844
1997 Csa-19, a radiation-responsive human gene, identified by an unbiased two-gel cDNA library screening method in human cancer cells. Oncogene 14 9223668
2017 miR-181c protects CsA-induced renal damage and fibrosis through inhibiting EMT. FEBS letters 13 28976551
2015 Inhibition of senescence and promotion of the proliferation of chondrocytes from articular cartilage by CsA and FK506 involves inhibition of p38MAPK. Mechanisms of ageing and development 13 26704447
2012 CsA improves the trophoblasts invasiveness through strengthening the cross-talk of trophoblasts and decidual stromal cells mediated by CXCL12 and CD82 in early pregnancy. International journal of clinical and experimental pathology 13 22670173
2010 High carriers frequency of an apparently ancient founder mutation p.Tyr322X in the ERCC8 gene responsible for Cockayne syndrome among Christian Arabs in Northern Israel. American journal of medical genetics. Part A 13 21108394
2017 A novel gingival overgrowth mouse model induced by the combination of CsA and ligature-induced inflammation. Journal of immunological methods 12 28274836
2014 IL-15 is decreased upon CsA and FK506 treatment of acute rejection following heart transplantation in mice. Molecular medicine reports 12 25333459
1995 Identification of genes downregulated in the thymus by cyclosporin-A: preliminary characterization of clone CSA-19. Molecular immunology 12 7609734
1986 Production of erythroid burst-promoting activity (BPA) and granulocyte-monocyte colony-stimulating activity (GM-CSA) by isolated human T-lymphocyte subpopulations. Experimental hematology 12 3488227