Smad6 inhibits non-canonical TGF-beta 1 signalling by recruiting the deubiquitinase A20 to TRAF6
DC Field | Value | Language |
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dc.contributor.author | Jung, Su Myung | - |
dc.contributor.author | Lee, Ji-Hyung | - |
dc.contributor.author | Park, Jinyoung | - |
dc.contributor.author | Oh, Young Sun | - |
dc.contributor.author | Lee, Sung Kyun | - |
dc.contributor.author | Park, Jin Seok | - |
dc.contributor.author | Lee, Youn Sook | - |
dc.contributor.author | Kim, Jun Hwan | - |
dc.contributor.author | Lee, Jae Young | - |
dc.contributor.author | Bae, Yoe-Sik | - |
dc.contributor.author | Koo, Seung-Hoi | - |
dc.contributor.author | Kim, Seong-Jin | - |
dc.contributor.author | Park, Seok Hee | - |
dc.date.accessioned | 2021-09-05T20:37:42Z | - |
dc.date.available | 2021-09-05T20:37:42Z | - |
dc.date.created | 2021-06-15 | - |
dc.date.issued | 2013-10 | - |
dc.identifier.issn | 2041-1723 | - |
dc.identifier.uri | https://scholar.korea.ac.kr/handle/2021.sw.korea/101995 | - |
dc.description.abstract | Transforming growth factor (TGF)-beta, a pivotal cytokine involved in a variety of cellular functions, transmits signals through Smad-dependent canonical and Smad-independent noncanonical pathways. In contrast to the canonical TGF-beta pathway, it is unknown how noncanonical TGF-beta pathways are negatively regulated. Here we demonstrate that the inhibitory Smad Smad6, but not Smad7, negatively regulates TGF-beta 1-induced activation of the TRAF6-TAK1-p38 MAPK/JNK pathway, a noncanonical TGF-beta pathway. TGF-beta 1-induced Smad6 abolishes K63-linked polyubiquitination of TRAF6 by recruiting the A20 deubiquitinating enzyme in AML-12 mouse liver cells and primary hepatocytes. In addition, the knockdown of Smad6 or A20 in an animal model or cell culture system maintains TAK1 and p38 MAPK/JNK phosphorylation and increases apoptosis, emphasizing the crucial role of the Smad6-A20 axis in negative regulation of the TGF-beta 1-TRAF6-TAK1-p38 MAPK/JNK pathway. Therefore, our findings provide insight into the molecular mechanisms underlying negative regulation of noncanonical TGF-beta pathways. | - |
dc.language | English | - |
dc.language.iso | en | - |
dc.publisher | NATURE PUBLISHING GROUP | - |
dc.subject | NF-KAPPA-B | - |
dc.subject | TGF-BETA RECEPTOR | - |
dc.subject | GROWTH-FACTOR-BETA | - |
dc.subject | ZINC-FINGER 7 | - |
dc.subject | PROTECTS MICE | - |
dc.subject | LINEAR POLYUBIQUITIN | - |
dc.subject | UBIQUITIN-BINDING | - |
dc.subject | TUMOR-SUPPRESSOR | - |
dc.subject | HUMAN-DISEASE | - |
dc.subject | ACTIVATION | - |
dc.title | Smad6 inhibits non-canonical TGF-beta 1 signalling by recruiting the deubiquitinase A20 to TRAF6 | - |
dc.type | Article | - |
dc.contributor.affiliatedAuthor | Koo, Seung-Hoi | - |
dc.identifier.doi | 10.1038/ncomms3562 | - |
dc.identifier.scopusid | 2-s2.0-84899604555 | - |
dc.identifier.wosid | 000326470400006 | - |
dc.identifier.bibliographicCitation | NATURE COMMUNICATIONS, v.4 | - |
dc.relation.isPartOf | NATURE COMMUNICATIONS | - |
dc.citation.title | NATURE COMMUNICATIONS | - |
dc.citation.volume | 4 | - |
dc.type.rims | ART | - |
dc.type.docType | Article | - |
dc.description.journalClass | 1 | - |
dc.description.journalRegisteredClass | scie | - |
dc.description.journalRegisteredClass | scopus | - |
dc.relation.journalResearchArea | Science & Technology - Other Topics | - |
dc.relation.journalWebOfScienceCategory | Multidisciplinary Sciences | - |
dc.subject.keywordPlus | NF-KAPPA-B | - |
dc.subject.keywordPlus | TGF-BETA RECEPTOR | - |
dc.subject.keywordPlus | GROWTH-FACTOR-BETA | - |
dc.subject.keywordPlus | ZINC-FINGER 7 | - |
dc.subject.keywordPlus | PROTECTS MICE | - |
dc.subject.keywordPlus | LINEAR POLYUBIQUITIN | - |
dc.subject.keywordPlus | UBIQUITIN-BINDING | - |
dc.subject.keywordPlus | TUMOR-SUPPRESSOR | - |
dc.subject.keywordPlus | HUMAN-DISEASE | - |
dc.subject.keywordPlus | ACTIVATION | - |
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