Disease relevance of CABIN1

• We have previously characterized the structure of a gene in A-172 human glioma cells that encodes a 190-kDa EGFR mutant with tandem duplication of the tyrosine kinase (TK) and calcium-mediated internalization (CAIN) domains [1].
• Oxidative stress in kidney transplant patients with calcineurin inhibitor-induced hypertension: effect of ramipril [2].
• CONCLUSIONS: The results explain late rejection after rapid calcineurin inhibitor withdrawal or reduction, and illustrate the potential use of SCID mice as a surrogate model to study graft outcome by determination levels of gene expression and sensitivity to immunosuppressive agents in the in vivo alloresponse [3].
• Reducing the dose of a calcineurin inhibitor, or using protocols without calcineurin inhibition may ultimately minimize the risk of drug toxicity and improve allograft and patient survival [4].
• Pimecrolimus is a calcineurin inhibitor developed for the topical therapy of inflammatory skin diseases, particularly atopic dermatitis (AD) [5].

Psychiatry related information on CABIN1

• Recently, Olsson and Cain (2000, Chem. Senses, 25: 493) introduced a psychometric method which, for the first time, allows the standardized determination of odor quality discrimination (OQD) thresholds [6].
• The review, which is largely based on presentations given by Dr. Richard Doty and Dr. William Cain, concludes by discussing the importance of the psychophysical approach, which considers physiochemical, subject, experimental, and cognitive/ psychological factors, for research in the chemical senses [7].

High impact information on CABIN1

• Several MEF2 co-repressors, such as Cabin1/Cain and class II histone deacetylases (HDACs), have been identified [8].
• Here we report a crystal structure of the MADS-box/MEF2S domain of human MEF2B bound to a motif of the transcriptional co-repressor Cabin1 and DNA at 2.2 A resolution [8].
• Sequence-specific recruitment of transcriptional co-repressor Cabin1 by myocyte enhancer factor-2 [8].
• TCR engagement led to an increase in intracellular calcium concentration and the dissociation of MEF2 from Cabin1, as a result of competitive binding of activated calmodulin to Cabin1 [9].
• Cabin 1, a negative regulator for calcineurin signaling in T lymphocytes [10].

Chemical compound and disease context of CABIN1

• We did a randomised controlled trial of mycophenolate mofetil monotherapy in liver transplant patients who developed renal failure associated with calcineurin-inhibitor (ciclosporin or tacrolimus) immunosuppressive therapy [11].
• By limiting the time of NFAT activation in normal control cells using the calcineurin inhibitor cyclosporin A, we were able to mimic the cytokine expression pattern in SCID T cells, suggesting that the expression of different cytokine genes is differentially regulated by the duration of NFAT residence in the nucleus [12].
• Hyperuricemia and gout have been associated with the use of the calcineurin inhibitor, cyclosporine [13].
• CONCLUSIONS: Dietary supplementation with L-arginine and canola oil is a safe, inexpensive, and unique treatment, which is associated with decreased rejection rates and CNI toxicity after the first month in renal transplant patients [14].
• 4. The use of calcineurin inhibitor (CNI)-based immunosuppression is an important factor in the development of chronic kidney disease, and the use of mycophenolic acid- or sirolimus-based immunosuppression with reduced-dose CNI may be of benefit [15].

Biological context of CABIN1

• The calcineurin-binding protein cain is a negative regulator of synaptic vesicle endocytosis [16].
• We further describe missense mutations in the CABIN1 gene that are specific to samples from schwannomatosis and NF2 and make this gene a plausible candidate for contributing to the pathogenesis of these disorders [17].
• The corresponding transcripts in KE and A-1235 cells contain 1053 additional nucleotides representing an in-frame duplication of exons 18 through 25 which encode the entire TK region and a portion of the CAIN domain [1].
• Thapsigargin-induced apoptosis involves Cabin1-MEF2-mediated induction of Nur77 [18].
• The pathophysiology of renal dysfunction is in part due to calcineurin inhibitor-induced renal vasoconstriction, through activation of the intrarenal renin-angiotensin system, TGF-beta1 upregulation and TGF-beta1 gene polymorphisms [19].

Anatomical context of CABIN1

• METHODS: We examined the apoptotic effects of the calcineurin inhibitor cyclosporine A and mTOR inhibitor rapamycin on the apoptotic alterations that occur in allospecifically activated human lymphocytes in a one-way mixed lymphocyte culture (MLC) [20].
• Calcineurin inhibitor effects on growth and phenotype of human airway epithelial cells in vitro [21].
• Moreover, in favour of non-endotoxin-mediated white cell activation, the calcineurin inhibitor, cyclosporin-A, which did not alter endotoxin-induced TNF-alpha production, decreased TNF-alpha produced by unstimulated cultured cells in patients to values not significantly greater than those in controls [22].
• Calmodulin-dependent protein kinase IV regulates nuclear export of Cabin1 during T-cell activation [23].
• Inherent calcineurin inhibitor FKBP38 targets Bcl-2 to mitochondria and inhibits apoptosis [24].

Associations of CABIN1 with chemical compounds

• CONCLUSION: Our data show that combining a calcineurin inhibitor or prednisone with mAbs designed to block costimulatory signals does not antagonize the immunosuppressive efficacy of these mAbs [25].
• Kinetic profiles of IL-2 mRNA expression also revealed individually distinct degrees of calcineurin inhibitor sensitivity in patients undergoing tacrolimus or CsA monotherapy before living-donor kidney transplantation [26].
• CONCLUSION: Collectively, these findings support the utility of combined treatment with captopril and CsA in the multitherapeutic management of organ transplant and, possibly, a strategy to decrease the dose of the calcineurin inhibitor in kidney-transplant recipients [27].
• The enhancement of IL-4 production by BPA or NP was significantly reduced by nitrendipine, a blocker of Ca2+ influx, and by FK506, a calcineurin inhibitor [28].
• Cohort one received a regimen of mycophenolate mofetil, prednisone, and a calcineurin inhibitor [29].

Physical interactions of CABIN1

• The overall binding mode is similar to that seen in the Cabin1/MEF2/DNA complex [30].
• CsA is a calcineurin inhibitor that binds to cyclophilins and inhibits transcription of interleukin 2 in T cells, thereby preventing proliferation of activated T cells [31].

Regulatory relationships of CABIN1

• We report that Cabin1 represses MEF2 by two distinct mechanisms [32].
• CONCLUSIONS: Our results suggest an individual degree of calcineurin inhibitor sensitivity of activated whole-blood lymphocytes based on IL-2 mRNA expression [26].
• BACKGROUND: Renal failure induced by calcineurin-inhibitor agents is a common complication of lung transplantation [33].
• Calcineurin inhibitor-induced nephrotoxicity and renal expression of P-glycoprotein [34].
• Calcineurin inhibitor-induced irreversible neuropathic pain after allogeneic hematopoietic stem cell transplantation [35].

Other interactions of CABIN1

• Immunosuppression consisted of an IL-2-receptor antibody, calcineurin inhibitor, mycophenolate mofetil, and corticosteroids [36].
• In the second candidate region spanning GSTT1 and CABIN1 genes, we observed a frequent copy number polymorphism at the GSTT1 locus [17].
• The role of calcineurin inhibitor in the formation of autoantibodies to ADAMTS13 remains to be explored [37].
• Most interestingly, the calcineurin inhibitor, FK506, consistently inhibited CD3/CD28-induced CXCR6 down-regulation [38].
• Multivariate logistic regression and Cox analysis showed that the calcineurin inhibitor used, pre-transplant BMI and adiponectin were predictors of NODAT [39].
• The Gal4-Cabin1-(501-900) alone repressed a constitutively active Gal4-tk-promoter, indicating that Cabin1 recruits SUV39H1 and represses transcriptional activity [40].

Analytical, diagnostic and therapeutic context of CABIN1

• The calcineurin inhibitor cyclosporine (CsA) induces a fibrogenic response that may lead to scarring of the renal allograft [41].
• Age, gender, time after transplantation, calcineurin inhibitor total dosage, number of teeth, and sulcus bleeding index were analyzed [42].
• Excellent results with calcineurin inhibitor-free initial immunosuppression in old recipients of old kidneys [43].
• Current success in organ transplantation is dependent upon the use of calcineurin-inhibitor-based immunosuppressive regimens [44].
• Standard immunosuppression consisted of calcineurin inhibitor-based triple drug therapy with or without ATG or IL2 receptor antagonist induction [45].

References