钙调神经磷酸酶
NFAT公司
肽
磷酸酶
生物化学
磷酸化
化学
分子生物学
生物
转录因子
细胞生物学
移植
医学
基因
外科
作者
Sangho Lee,Han‐Teo Lee,Young Ah Kim,Il-Hwan Lee,Seong‐Jun Kang,Kyeongpyo Sim,Chung‐Gyu Park,Kyungho Choi,Hong‐Duk Youn
标识
DOI:10.1038/s12276-022-00772-6
摘要
The C-terminal fragment of CABIN1 interacts with calcineurin and represses the transcriptional activity of the nuclear factor of activated T cells (NFAT). However, the specific sequences and mechanisms through which it binds to calcineurin are unclear. This study determined that decameric peptide (CABIN1 residues 2146-2155) is minimally required for binding to calcineurin. This peptide contains a unique "PPTP" C-terminal sequence and a "PxIxIT" N-terminal motif. Furthermore, p38MAPK phosphorylated the threonine residue of the "PPTP" sequence under physiological conditions, dramatically enhancing the peptide's binding affinity to calcineurin. Therefore, the CABIN1 peptide inhibited the calcineurin-NFAT pathway and the activation of T cells more efficiently than the VIVIT peptide without affecting calcineurin's phosphatase activity. The CABIN1 peptide could thus be a more potent calcineurin inhibitor and provide therapeutic opportunities for various diseases caused by the calcineurin-NFAT pathway.
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