Overexpression of prohibitin-1 inhibits RANKL-induced activation of p38-Elk-1-SRE signaling axis blocking MKK6 activity
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 o...
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| Veröffentlicht in: | Biochemical and biophysical research communications 2015-08, Vol.463 (4), p.1028-1033 |
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| container_title | Biochemical and biophysical research communications |
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| creator | Lee, Chang Hoon Choi, Sik-Won Kim, Ju-Young Kim, Seong Hwan Yoon, Kwon-Ha Oh, Jaemin Lee, Myeung Su |
| description | 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.
[Display omitted]
•We first investigated the functional involvement of prohibitin-1 in osteoclast differentiation.•Our data demonstrate for the first time that prohibitin-1 inhibits osteoclastogenesis.•Prohibitin-1 acts as an inhibitor of c-Fos and NFATc1 activation.•Prohibitin-1 inhibits activation of the MKK6-p38-Elk-1-c-Fos SRE signaling axis.•Prohibitin-1 deserves new evaluation as a potential treatment target in various bone diseases. |
| doi_str_mv | 10.1016/j.bbrc.2015.06.053 |
| format | Article |
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[Display omitted]
•We first investigated the functional involvement of prohibitin-1 in osteoclast differentiation.•Our data demonstrate for the first time that prohibitin-1 inhibits osteoclastogenesis.•Prohibitin-1 acts as an inhibitor of c-Fos and NFATc1 activation.•Prohibitin-1 inhibits activation of the MKK6-p38-Elk-1-c-Fos SRE signaling axis.•Prohibitin-1 deserves new evaluation as a potential treatment target in various bone diseases.</description><identifier>ISSN: 0006-291X</identifier><identifier>EISSN: 1090-2104</identifier><identifier>DOI: 10.1016/j.bbrc.2015.06.053</identifier><identifier>PMID: 26079882</identifier><language>eng</language><publisher>United States: Elsevier Inc</publisher><subject>c-Fos ; Elk-1 ; ets-Domain Protein Elk-1 - metabolism ; Humans ; MAP Kinase Kinase 6 - antagonists & inhibitors ; MAP Kinase Kinase 6 - metabolism ; MKK6 ; Osteoclastogenesis ; p38 ; p38 Mitogen-Activated Protein Kinases - metabolism ; Prohibitin-1 ; RANK Ligand - metabolism ; Repressor Proteins - metabolism</subject><ispartof>Biochemical and biophysical research communications, 2015-08, Vol.463 (4), p.1028-1033</ispartof><rights>2015 Elsevier Inc.</rights><rights>Copyright © 2015 Elsevier Inc. All rights reserved.</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c459t-5f407ea4f561e549365f07658b780ad5b6b23a811b86eb090f34908bc73261263</citedby><cites>FETCH-LOGICAL-c459t-5f407ea4f561e549365f07658b780ad5b6b23a811b86eb090f34908bc73261263</cites><orcidid>0000-0002-8001-5653</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktohtml>$$Uhttps://dx.doi.org/10.1016/j.bbrc.2015.06.053$$EHTML$$P50$$Gelsevier$$H</linktohtml><link.rule.ids>314,780,784,3548,27922,27923,45993</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/26079882$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Lee, Chang Hoon</creatorcontrib><creatorcontrib>Choi, Sik-Won</creatorcontrib><creatorcontrib>Kim, Ju-Young</creatorcontrib><creatorcontrib>Kim, Seong Hwan</creatorcontrib><creatorcontrib>Yoon, Kwon-Ha</creatorcontrib><creatorcontrib>Oh, Jaemin</creatorcontrib><creatorcontrib>Lee, Myeung Su</creatorcontrib><title>Overexpression of prohibitin-1 inhibits RANKL-induced activation of p38-Elk-1-SRE signaling axis blocking MKK6 activity</title><title>Biochemical and biophysical research communications</title><addtitle>Biochem Biophys Res Commun</addtitle><description>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.
[Display omitted]
•We first investigated the functional involvement of prohibitin-1 in osteoclast differentiation.•Our data demonstrate for the first time that prohibitin-1 inhibits osteoclastogenesis.•Prohibitin-1 acts as an inhibitor of c-Fos and NFATc1 activation.•Prohibitin-1 inhibits activation of the MKK6-p38-Elk-1-c-Fos SRE signaling axis.•Prohibitin-1 deserves new evaluation as a potential treatment target in various bone diseases.</description><subject>c-Fos</subject><subject>Elk-1</subject><subject>ets-Domain Protein Elk-1 - metabolism</subject><subject>Humans</subject><subject>MAP Kinase Kinase 6 - antagonists & inhibitors</subject><subject>MAP Kinase Kinase 6 - metabolism</subject><subject>MKK6</subject><subject>Osteoclastogenesis</subject><subject>p38</subject><subject>p38 Mitogen-Activated Protein Kinases - metabolism</subject><subject>Prohibitin-1</subject><subject>RANK Ligand - metabolism</subject><subject>Repressor Proteins - metabolism</subject><issn>0006-291X</issn><issn>1090-2104</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2015</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqFkcFu1DAQhi0EotvCC3BAOXJxmHFix5a4VNXSol2oVFqJm2U7TvE2myx2dtu-PV625Qgnj6Xv_6WZj5B3CCUCio-r0troSgbISxAl8OoFmSEooAyhfklmACAoU_jjiByntAJArIV6TY6YgEZJyWbk_nLno3_YRJ9SGIdi7IpNHH8GG6YwUCzC8GdOxdXpt8WShqHdOt8Wxk1hZ6bnRCXpvL-jSL9fzYsUbgfTh-G2MA8hFbYf3d3-93WxEIdgmB7fkFed6ZN_-_SekJvP8-uzC7q8PP9ydrqkruZqoryrofGm7rhAz2tVCd5BI7i0jQTTcissq4xEtFJ4m1fvqlqBtK6pmEAmqhPy4dCbt_q19WnS65Cc73sz-HGbNDa1kI1qOP8_KhTPOIomo-yAujimFH2nNzGsTXzUCHrvRq_03o3eu9EgdHaTQ--f-rd27du_kWcZGfh0AHw-yC74qJMLfsj3DtG7Sbdj-Ff_b8aqnhw</recordid><startdate>20150807</startdate><enddate>20150807</enddate><creator>Lee, Chang Hoon</creator><creator>Choi, Sik-Won</creator><creator>Kim, Ju-Young</creator><creator>Kim, Seong Hwan</creator><creator>Yoon, Kwon-Ha</creator><creator>Oh, Jaemin</creator><creator>Lee, Myeung Su</creator><general>Elsevier Inc</general><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7X8</scope><scope>7QP</scope><orcidid>https://orcid.org/0000-0002-8001-5653</orcidid></search><sort><creationdate>20150807</creationdate><title>Overexpression of prohibitin-1 inhibits RANKL-induced activation of p38-Elk-1-SRE signaling axis blocking MKK6 activity</title><author>Lee, Chang Hoon ; Choi, Sik-Won ; Kim, Ju-Young ; Kim, Seong Hwan ; Yoon, Kwon-Ha ; Oh, Jaemin ; Lee, Myeung Su</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c459t-5f407ea4f561e549365f07658b780ad5b6b23a811b86eb090f34908bc73261263</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2015</creationdate><topic>c-Fos</topic><topic>Elk-1</topic><topic>ets-Domain Protein Elk-1 - metabolism</topic><topic>Humans</topic><topic>MAP Kinase Kinase 6 - antagonists & inhibitors</topic><topic>MAP Kinase Kinase 6 - metabolism</topic><topic>MKK6</topic><topic>Osteoclastogenesis</topic><topic>p38</topic><topic>p38 Mitogen-Activated Protein Kinases - metabolism</topic><topic>Prohibitin-1</topic><topic>RANK Ligand - metabolism</topic><topic>Repressor Proteins - metabolism</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Lee, Chang Hoon</creatorcontrib><creatorcontrib>Choi, Sik-Won</creatorcontrib><creatorcontrib>Kim, Ju-Young</creatorcontrib><creatorcontrib>Kim, Seong Hwan</creatorcontrib><creatorcontrib>Yoon, Kwon-Ha</creatorcontrib><creatorcontrib>Oh, Jaemin</creatorcontrib><creatorcontrib>Lee, Myeung Su</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>MEDLINE - Academic</collection><collection>Calcium & Calcified Tissue Abstracts</collection><jtitle>Biochemical and biophysical research communications</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Lee, Chang Hoon</au><au>Choi, Sik-Won</au><au>Kim, Ju-Young</au><au>Kim, Seong Hwan</au><au>Yoon, Kwon-Ha</au><au>Oh, Jaemin</au><au>Lee, Myeung Su</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Overexpression of prohibitin-1 inhibits RANKL-induced activation of p38-Elk-1-SRE signaling axis blocking MKK6 activity</atitle><jtitle>Biochemical and biophysical research communications</jtitle><addtitle>Biochem Biophys Res Commun</addtitle><date>2015-08-07</date><risdate>2015</risdate><volume>463</volume><issue>4</issue><spage>1028</spage><epage>1033</epage><pages>1028-1033</pages><issn>0006-291X</issn><eissn>1090-2104</eissn><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.
[Display omitted]
•We first investigated the functional involvement of prohibitin-1 in osteoclast differentiation.•Our data demonstrate for the first time that prohibitin-1 inhibits osteoclastogenesis.•Prohibitin-1 acts as an inhibitor of c-Fos and NFATc1 activation.•Prohibitin-1 inhibits activation of the MKK6-p38-Elk-1-c-Fos SRE signaling axis.•Prohibitin-1 deserves new evaluation as a potential treatment target in various bone diseases.</abstract><cop>United States</cop><pub>Elsevier Inc</pub><pmid>26079882</pmid><doi>10.1016/j.bbrc.2015.06.053</doi><tpages>6</tpages><orcidid>https://orcid.org/0000-0002-8001-5653</orcidid></addata></record> |
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| subjects | c-Fos Elk-1 ets-Domain Protein Elk-1 - metabolism Humans MAP Kinase Kinase 6 - antagonists & inhibitors MAP Kinase Kinase 6 - metabolism MKK6 Osteoclastogenesis p38 p38 Mitogen-Activated Protein Kinases - metabolism Prohibitin-1 RANK Ligand - metabolism Repressor Proteins - metabolism |
| title | Overexpression of prohibitin-1 inhibits RANKL-induced activation of p38-Elk-1-SRE signaling axis blocking MKK6 activity |
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