@article{oai:nagoya.repo.nii.ac.jp:00001368, author = {CAO, Xia and KAMBE, Fukushi and SEO, Hisao}, issue = {1/2}, journal = {Environmental medicine : annual report of the Research Institute of Environmental Medicine, Nagoya University}, month = {Dec}, note = {We identified ZAKI-4 as a thyroid hormone (T3) responsive gene in human skin fibroblasts. Our recent study revealed that two ZAKI-4 isoforms, α and β, are generated from a single gene on chromosome 6. Only expression of α is increased by T3, while that of β is not affected. Both isoforms belong to a family of proteins containing a conserved motif, which interacts with calcineurin and inhibits its activity. Recently, expression of a mouse homologue of the ZAKI-4 family gene (MCIP1) is shown to be induced by the activation of calcineurin in myocytes. We thus studied whether ZAKI-4 expression is also regulated by calcineurin-mediated pathway. Northern blot analysis revealed activation of calcineurin by ionomycin/phorbol 12-myristate 13-acetate (PMA) did not increase the expression of both isoforms. In addition, either basal expression of the two isoforms or T3-induced ZAKI-4α expression was not affected by FK506, a specific calcineurin inhibitor, suggesting the activation of calcineurin is not involved in ZAKI-4 regulation. However, cyclosporin A (CsA), another inhibitor of calcineurin decreased the basal expression of ZAKI-4α. Furthermore, T3-mediated increase of ZAKI-4α was completely blocked by CsA, but not by FK506. It is thus indicated that the two isoforms are differentially regulated, and the regulation of ZAKI-4α involves a CsA-sensitive pathway, which is independent of calcineurin activation., 国立情報学研究所で電子化したコンテンツを使用している。}, pages = {40--42}, title = {Cyclosporin A (CsA)-sensitive Pathway for the Induction of ZAKI-4 Expression by Thyroid Hormone}, volume = {46}, year = {2002} }