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Article: F-box only protein 31 (FBX031) negatively regulates p38 mitogen-activated protein kinase (MAPK) signaling by mediating lysine 48-linked ubiquitination and degradation of mitogen-activated protein kinase kinase 6 (MKK6)

TitleF-box only protein 31 (FBX031) negatively regulates p38 mitogen-activated protein kinase (MAPK) signaling by mediating lysine 48-linked ubiquitination and degradation of mitogen-activated protein kinase kinase 6 (MKK6)
Authors
KeywordsApoptosis
Cancer
F-box Protein
FBXO31
MKK6
Issue Date2014
PublisherAmerican Society for Biochemistry and Molecular Biology, Inc. The Journal's web site is located at http://www.jbc.org/
Citation
Journal of Biological Chemistry, 2014, v. 289 n. 31, p. 21508-21518 How to Cite?
AbstractThe p38 MAPK signal transduction pathway plays an important role in inflammatory and stress responses. MAPKK6 (MKK6), a dual specificity protein kinase, is a p38 activator. Activation of the MKK6-p38 pathway is kept in check by multiple layers of regulations, including autoinhibition, dimerization, scaffold proteins, and Lys-63-linked polyubiquitination. However, the mechanisms underlying deactivation of MKK6-p38, which is crucial for maintaining the magnitude and duration of signal transduction, are not well understood. Lys-48-linked ubiquitination, which marks substrates for proteasomal degradation, is an important negative posttranslational regulatory machinery for signal pathway transduction. Here we report that the accumulation of F-box only protein 31 (FBXO31), a component of Skp1 · Cul1 · F-box protein E3 ligase, negatively regulated p38 activation in cancer cells upon genotoxic stresses. Our results show that FBXO31 binds to MKK6 and mediates its Lys-48-linked polyubiquitination and degradation, thereby functioning as a negative regulator of MKK6-p38 signaling and protecting cells from stress-induced cell apoptosis. Taken together, our findings uncover a new mechanism of deactivation of MKK6-p38 and substantiate a novel regulatory role of FBXO31 in stress response.
Persistent Identifierhttp://hdl.handle.net/10722/200450
ISSN
2015 Impact Factor: 4.258
2015 SCImago Journal Rankings: 3.151
PubMed Central ID
ISI Accession Number ID

 

DC FieldValueLanguage
dc.contributor.authorLiu, Jen_US
dc.contributor.authorHan, Len_US
dc.contributor.authorLi, Ben_US
dc.contributor.authorYang, Jen_US
dc.contributor.authorHuen, MSYen_US
dc.contributor.authorPan, Xen_US
dc.contributor.authorTsao, GSWen_US
dc.contributor.authorCheung, Aen_US
dc.date.accessioned2014-08-21T06:46:35Z-
dc.date.available2014-08-21T06:46:35Z-
dc.date.issued2014en_US
dc.identifier.citationJournal of Biological Chemistry, 2014, v. 289 n. 31, p. 21508-21518en_US
dc.identifier.issn0021-9258-
dc.identifier.urihttp://hdl.handle.net/10722/200450-
dc.description.abstractThe p38 MAPK signal transduction pathway plays an important role in inflammatory and stress responses. MAPKK6 (MKK6), a dual specificity protein kinase, is a p38 activator. Activation of the MKK6-p38 pathway is kept in check by multiple layers of regulations, including autoinhibition, dimerization, scaffold proteins, and Lys-63-linked polyubiquitination. However, the mechanisms underlying deactivation of MKK6-p38, which is crucial for maintaining the magnitude and duration of signal transduction, are not well understood. Lys-48-linked ubiquitination, which marks substrates for proteasomal degradation, is an important negative posttranslational regulatory machinery for signal pathway transduction. Here we report that the accumulation of F-box only protein 31 (FBXO31), a component of Skp1 · Cul1 · F-box protein E3 ligase, negatively regulated p38 activation in cancer cells upon genotoxic stresses. Our results show that FBXO31 binds to MKK6 and mediates its Lys-48-linked polyubiquitination and degradation, thereby functioning as a negative regulator of MKK6-p38 signaling and protecting cells from stress-induced cell apoptosis. Taken together, our findings uncover a new mechanism of deactivation of MKK6-p38 and substantiate a novel regulatory role of FBXO31 in stress response.-
dc.languageengen_US
dc.publisherAmerican Society for Biochemistry and Molecular Biology, Inc. The Journal's web site is located at http://www.jbc.org/-
dc.relation.ispartofJournal of Biological Chemistryen_US
dc.rightsJournal of Biological Chemistry. Copyright © American Society for Biochemistry and Molecular Biology, Inc.-
dc.rightsThis research was originally published in Journal of Biological Chemistry. Liu, J (et al.). F-box only protein 31 (FBX031) negatively regulates p38 mitogen-activated protein kinase (MAPK) signaling by mediating lysine 48-linked ubiquitination and degradation of mitogen-activated protein kinase kinase 6 (MKK6). Journal of Biological Chemistry. 2014. Vol 289: p. 21508-21518. © the American Society for Biochemistry and Molecular Biology-
dc.subjectApoptosis-
dc.subjectCancer-
dc.subjectF-box Protein-
dc.subjectFBXO31-
dc.subjectMKK6-
dc.titleF-box only protein 31 (FBX031) negatively regulates p38 mitogen-activated protein kinase (MAPK) signaling by mediating lysine 48-linked ubiquitination and degradation of mitogen-activated protein kinase kinase 6 (MKK6)en_US
dc.typeArticleen_US
dc.identifier.emailLiu, J: liuj614@hku.hken_US
dc.identifier.emailLi, B: libinhku@hkucc.hku.hken_US
dc.identifier.emailYang, J: jiesarah@hku.hken_US
dc.identifier.emailHuen, MSY: huen.michael@hku.hken_US
dc.identifier.emailTsao, GSW: gswtsao@hku.hken_US
dc.identifier.emailCheung, A: lmcheung@hku.hken_US
dc.identifier.authorityHuen, MSY=rp01336en_US
dc.identifier.authorityTsao, GSW=rp00399en_US
dc.description.naturelink_to_subscribed_fulltext-
dc.identifier.doi10.1074/jbc.M114.560342en_US
dc.identifier.pmid24936062-
dc.identifier.pmcidPMC4118112-
dc.identifier.scopuseid_2-s2.0-84905390264-
dc.identifier.hkuros234313en_US
dc.identifier.volume289en_US
dc.identifier.issue31-
dc.identifier.spage21508en_US
dc.identifier.epage21518en_US
dc.identifier.isiWOS:000340558300027-
dc.publisher.placeUnited States-

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