Cyclophilin A regulates the apoptosis of A549 cells by stabilizing Twist1 protein

Abstract

ABSTRACT Cyclophilin A (CypA, also known as PPIA) is an essential member of the immunophilin family. As an intracellular target of the immunosuppressive drug cyclosporin A (CsA) or a peptidyl-prolyl cis/trans isomerase (PPIase), it catalyzes the cis-trans isomerization of proline amidic peptide bonds, through which it regulates a variety of biological processes, such as intracellular signaling, transcription and apoptosis. In this study, we found that intracellular CypA enhanced Twist1 phosphorylation at Ser68 and inhibited apoptosis in A549 cells. Mechanistically, CypA could mediate the phosphorylation of Twist1 at Ser68 via p38 mitogen-activated protein kinase (also known as MAPK14), which inhibited its ubiquitylation-mediated degradation. In addition, CypA increased interaction between Twist1 and p65 (also known as RELA), as well as nuclear accumulation of the Twist1-p65 complex, which regulated Twist1-dependent expression of CDH1 and CDH2. Our findings collectively indicate the role of CypA in Twist1-mediated apoptosis of A549 cells through stabilizing Twist1 protein.