2. Academic Validation
  3. Cyclophilin A regulates JNK/p38-MAPK signaling through its physical interaction with ASK1

Cyclophilin A regulates JNK/p38-MAPK signaling through its physical interaction with ASK1

  • Biochem Biophys Res Commun. 2015 Aug 14;464(1):112-7. doi: 10.1016/j.bbrc.2015.06.078.
Hunsung Kim 1,  Yoojung Oh 1,  Kiyoon Kim 1,  Suyun Jeong 1,  Suk Chon 2,  Daehong Kim 3,  Min Hyung Jung 4,  Youngmi Kim Pak 5,  Joohun Ha 1,  Insug Kang 1,  Wonchae Choe 6
Affiliations

Affiliations

  • 1 Department of Biochemistry and Molecular Biology (BK21 project), Medical Research Center for Bioreaction to Reactive Oxygen Species and Biomedical Science Institute, School of Medicine, Kyung Hee University, Seoul 130-701, Republic of Korea.
  • 2 Department of Endocrinology and Metabolism, Kyung Hee University School of Medicine, Seoul, Republic of Korea.
  • 3 Molecular Imaging & Therapy Branch, National Cancer Center, 809 Madu1dong Ilsandonggu Goyangsi, Gyeonggydo 410-769, Republic of Korea.
  • 4 Department of Physiology, College of Medicine, Kyung Hee University, Seoul 130-731, Republic of Korea.
  • 5 Department of Obstetrics and Gynecology, School of Medicine, Kyung Hee University, Seoul 130-701, Republic of Korea.
  • 6 Department of Biochemistry and Molecular Biology (BK21 project), Medical Research Center for Bioreaction to Reactive Oxygen Species and Biomedical Science Institute, School of Medicine, Kyung Hee University, Seoul 130-701, Republic of Korea. Electronic address: [email protected].
PMID: 26095851 DOI: 10.1016/j.bbrc.2015.06.078
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.

Keywords

Apoptosis; Apoptosis signal-regulating kinase 1(ASK1); Cyclophilin A (CypA); Mitogen-activated protein kinase (MAPK); Oxidative-stress.

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