Reference - Detail
| RRC ID | 79241 |
|---|---|
| Author | Takasaki T, Bamba A, Kukita Y, Nishida A, Kanbayashi D, Hagihara K, Satoh R, Ishihara K, Sugiura R. |
| Title | Rcn1, the fission yeast homolog of human DSCR1, regulates arsenite tolerance independently from calcineurin. |
| Journal | Genes Cells |
| Abstract |
Calcineurin (CN) is a conserved Ca2+/calmodulin-dependent phosphoprotein phosphatase that plays a key role in Ca2+ signaling. Regulator of calcineurin 1 (RCAN1), also known as Down syndrome critical region gene 1 (DSCR1), interacts with calcineurin and inhibits calcineurin-dependent signaling in various organisms. Ppb1, the fission yeast calcineurin regulates Cl--homeostasis, and Ppb1 deletion induces MgCl2 hypersensitivity. Here, we characterize the conserved and novel roles of the fission yeast RCAN1 homolog rcn1+. Consistent with its role as an endogenous calcineurin inhibitor, Rcn1 overproduction reproduced the calcineurin-null phenotypes, including MgCl2 hypersensitivity and inhibition of calcineurin signaling upon extracellular Ca2+ stimuli as evaluated by the nuclear translocation and transcriptional activation of the calcineurin substrate Prz1. Notably, overexpression of rcn1+ causes hypersensitivity to arsenite, whereas calcineurin deletion induces arsenite tolerance, showing a phenotypic discrepancy between Rcn1 overexpression and calcineurin deletion. Importantly, although Rcn1 deletion induces modest sensitivities to arsenite and MgCl2 in wild-type cells, the arsenite tolerance, but not MgCl2 sensitivity, associated with Ppb1 deletion was markedly suppressed by Rcn1 deletion. Collectively, our findings reveal a previously unrecognized functional collaboration between Rcn1 and calcineurin, wherein Rcn1 not only negatively regulates calcineurin in the Cl- homeostasis, but also Rcn1 mediates calcineurin signaling to modulate arsenite cytotoxicity. |
| Published | 2024-5-7 |
| DOI | 10.1111/gtc.13122 |
| PMID | 38715219 |
| MeSH | Arsenites* / pharmacology Arsenites* / toxicity Calcineurin* / genetics Calcineurin* / metabolism DNA-Binding Proteins Humans Intracellular Signaling Peptides and Proteins / genetics Intracellular Signaling Peptides and Proteins / metabolism Muscle Proteins Schizosaccharomyces* / genetics Schizosaccharomyces* / metabolism Schizosaccharomyces pombe Proteins* / genetics Schizosaccharomyces pombe Proteins* / metabolism Signal Transduction |
| IF | 1.655 |
| Altmetric score |
オルトメトリクス指標項目
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| The most frequently cited source | X(Twitter) |
| Total number of mentions | 1 |
| Altmetric score changes over past 6months | 0.0 |
| Resource | |
| Yeast | FY9899 |