title: Overexpression of prohibitin-1 inhibits RANKL-induced activation of p38-Elk-1-SRE signaling axis blocking MKK6 activity.
abstract: Prohibitin-1 (PHB) regulates diverse cellular processes by controlling several signaling pathways. In this study, we investigated the functional involvement of PHB in osteoclast differentiation. PHB expression was time-dependently increased by RANKL in BMMs. However, the retroviral over-expression of PHB strongly inhibited the expression of c-Fos and NFATc1, and activation of p38-Elk-1-SRE signaling pathway. Anti-osteoclastogenic action of PHB was significantly inhibited by constitutively active forms of MKK6, but not Elk-1. Collectively, PHB negatively regulates the formation of mature osteoclasts via inhibition of MKK6 activity that affects the activation of the p38-Elk-1 signaling axis required for the expression of c-Fos and NFATc1.
authors.affiliation: Division of Rheumatology, Department of Internal Medicine, Wonkwang University, Iksan, Jeonbuk 570-749, Republic of Korea; Imaging Science-based Lung and Bone Diseases Research Center, Wonkwang University, Iksan, Jeonbuk 570-749, Republic of Korea.
authors.forename: Chang Hoon
authors.initials: CH
authors.lastname: Lee
authors.affiliation: Laboratory of Translational Therapeutics, Pharmacology Research Center, Bio-Organic Science Division, Korea Research Institute of Chemical Technology, Daejeon 305-600, Republic of Korea.
authors.forename: Sik-Won
authors.initials: SW
authors.lastname: Choi
authors.affiliation: Imaging Science-based Lung and Bone Diseases Research Center, Wonkwang University, Iksan, Jeonbuk 570-749, Republic of Korea.
authors.forename: Ju-Young
authors.initials: JY
authors.lastname: Kim
authors.affiliation: Laboratory of Translational Therapeutics, Pharmacology Research Center, Bio-Organic Science Division, Korea Research Institute of Chemical Technology, Daejeon 305-600, Republic of Korea.
authors.forename: Seong Hwan
authors.initials: SH
authors.lastname: Kim
authors.affiliation: Department of Radiology, School of Medicine, Wonkwang University, Iksan, Jeonbuk 570-749, Republic of Korea.
authors.forename: Kwon-Ha
authors.initials: KH
authors.lastname: Yoon
authors.affiliation: Imaging Science-based Lung and Bone Diseases Research Center, Wonkwang University, Iksan, Jeonbuk 570-749, Republic of Korea; Department of Anatomy, School of Medicine, Wonkwang University, Iksan, Jeonbuk 570-749, Republic of Korea. Electronic address: jmoh@wku.ac.kr.
authors.forename: Jaemin
authors.initials: J
authors.lastname: Oh
authors.affiliation: Division of Rheumatology, Department of Internal Medicine, Wonkwang University, Iksan, Jeonbuk 570-749, Republic of Korea; Imaging Science-based Lung and Bone Diseases Research Center, Wonkwang University, Iksan, Jeonbuk 570-749, Republic of Korea. Electronic address: ckhlms@wku.ac.kr.
authors.forename: Myeung Su
authors.initials: MS
authors.lastname: Lee
mesh_terms: D006801:Humans; D048669:MAP Kinase Kinase 6 / Q000037:antagonists & inhibitors* / Q000378:metabolism; D000091402:Prohibitins; D053245:RANK Ligand / Q000378:metabolism*; D012097:Repressor Proteins / Q000378:metabolism*; D050807:ets-Domain Protein Elk-1 / Q000378:metabolism*; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism*
chemical_list: C494112:ELK1 protein, human; C000717328:PHB protein, human; D000091402:Prohibitins; D053245:RANK Ligand; D012097:Repressor Proteins; C505688:TNFSF11 protein, human; D050807:ets-Domain Protein Elk-1; D048051:p38 Mitogen-Activated Protein Kinases; D048669:MAP Kinase Kinase 6; C482566:MAP2K6 protein, human
keywords: Elk-1; MKK6; Osteoclastogenesis; Prohibitin-1; c-Fos; p38