Overexpression of prohibitin-1 inhibits RANKL-induced activation of p38-Elk-1-SRE signaling axis blocking MKK6 activity

Biochem Biophys Res Commun. 2015 Aug 7;463(4):1028-33. doi: 10.1016/j.bbrc.2015.06.053. Epub 2015 Jun 12.

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.

Keywords: Elk-1; MKK6; Osteoclastogenesis; Prohibitin-1; c-Fos; p38.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Humans
  • MAP Kinase Kinase 6 / antagonists & inhibitors*
  • MAP Kinase Kinase 6 / metabolism
  • Prohibitins
  • RANK Ligand / metabolism*
  • Repressor Proteins / metabolism*
  • ets-Domain Protein Elk-1 / metabolism*
  • p38 Mitogen-Activated Protein Kinases / metabolism*

Substances

  • ELK1 protein, human
  • PHB protein, human
  • Prohibitins
  • RANK Ligand
  • Repressor Proteins
  • TNFSF11 protein, human
  • ets-Domain Protein Elk-1
  • p38 Mitogen-Activated Protein Kinases
  • MAP Kinase Kinase 6
  • MAP2K6 protein, human