Dephosphorylation of NFAT by Calcineurin inhibits Skp2-mediated degradation.
J Biochem
; 175(3): 235-244, 2024 Mar 04.
Article
em En
| MEDLINE
| ID: mdl-38030387
ABSTRACT
The transcription factor NFAT plays key roles in multiple biological activities, such as immune responses, tissue development and malignant transformation. NFAT is dephosphorylated by calcineurin, which is activated by intracellular calcium levels, and translocated into the nucleus, resulting in transcriptional activation. Calcineurin dephosphorylates various target proteins and regulates their functions. However, the regulation of NFAT degradation is largely unknown, and it is unclear whether calcineurin contributes to the stability of NFAT. We investigated the effect of calcineurin inhibition on NFAT protein stability and found that the dephosphorylation of NFAT by calcineurin promotes the NFAT stabilization, whereas calcineurin mutant that is defective in phosphatase activity was unable to stabilize NFAT. Increased intracellular calcium ion concentration, which is essential for calcineurin activation, also induced NFAT stability. In addition, we identified S-phase kinase associated protein 2 (Skp2), an F-box protein of the SCF ubiquitin ligase complex, as a factor mediating degradation of NFAT when calcineurin was depleted. In summary, these findings revealed that the dephosphorylation of NFAT by calcineurin protects NFAT from degradation by Skp2 and promotes its protein stability.
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Base de dados:
MEDLINE
Assunto principal:
Calcineurina
/
Fatores de Transcrição NFATC
Idioma:
En
Ano de publicação:
2024
Tipo de documento:
Article