| Literature DB >> 26095851 |
Hunsung Kim1, Yoojung Oh1, Kiyoon Kim1, Suyun Jeong1, Suk Chon2, Daehong Kim3, Min Hyung Jung4, Youngmi Kim Pak5, Joohun Ha1, Insug Kang1, Wonchae Choe6.
Abstract
Cyclophilin A (CypA), a member of the immunophilin family, is predominantly localized in the cytoplasm. The peptidylprolyl isomerase (PPIase) activity of CypA has been demonstrated to be involved in diverse cellular processes, including intracellular protein trafficking, mitochondrial function, pre-mRNA processing, and maintenance of multiprotein complex stability. In this study, we have demonstrated that CypA regulates apoptosis signaling-regulating kinase 1 (ASK1) through its direct binding. ASK1 is a member of MAPK kinase kinase (MAP3K) family, and selectively activates both JNK and p38 MAPK pathways. Here, we also report that CypA negatively regulates phosphorylation of ASK1 at Ser966, and that CypA reduces ASK1 and its downstream kinases of the JNK and p38 signaling. ASK1 is known to induce caspase-3 activation and apoptosis, and CypA inhibited ASK1-mediated apoptosis by decrease in caspase-3 activity under cellular stress conditions. Overall, we conclude that CypA negatively regulates ASK1 functions by its physical interaction with ASK1.Entities:
Keywords: Apoptosis; Apoptosis signal-regulating kinase 1(ASK1); Cyclophilin A (CypA); Mitogen-activated protein kinase (MAPK); Oxidative-stress
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Year: 2015 PMID： 26095851 DOI： 10.1016/j.bbrc.2015.06.078
Source DB: PubMed Journal: Biochem Biophys Res Commun ISSN： 0006-291X Impact factor: 3.575