Oncogenic mutation of AIMP2/p38 inhibits its tumor-suppresive interaction with Smurf2

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dc.contributor.authorD G Kim-
dc.contributor.authorJ Y Lee-
dc.contributor.authorJ H Lee-
dc.contributor.authorH Y Cho-
dc.contributor.authorB S Kang-
dc.contributor.authorSong-Yee Jang-
dc.contributor.authorMyung Hee Kim-
dc.contributor.authorM Guo-
dc.contributor.authorJ M Han-
dc.contributor.authorS J Kim-
dc.contributor.authorS Kim-
dc.date.accessioned2017-04-19T10:22:44Z-
dc.date.available2017-04-19T10:22:44Z-
dc.date.issued2016-
dc.identifier.issn00085472-
dc.identifier.uri10.1158/0008-5472.CAN-15-3255ko
dc.identifier.urihttps://oak.kribb.re.kr/handle/201005/13290-
dc.description.abstractAIMP2/p38 is a multifunctional tumor suppressor that normally resides in the cytosol as a scaffold protein of the multi-tRNA synthetase complex (MSC). One of the tumor-suppressive functions of AIMP2 is to facilitate ubiquitinmediated degradation of FUSE-binding protein (FBP, FUBP1), a transcriptional activator of c-Myc. However, the mechanism by which AIMP2 functions within this pathway and its significance in tumorigenesis are uncertain. Here, we report that Smurf2 is responsible for AIMP2-mediated ubiquitination of FBP, and a mutation in AIMP2 that inhibited its nuclear interaction with Smurf2 enhanced cellular transformation and tumorigenesis in vivo. Treatment of HeLa cells with TGFb resulted in the phosphorylation of AIMP2 on S156, a residue that is exposed on the embedded GST domain of AIMP2. We further found that phospho-AIMP2 dissociated from the MSC and translocated to the nucleus, where it bound to Smurf2, enhancing ubiquitination of FBP. AIMP2 also inhibited nuclear export of Smurf2 to sustain TGFβ signaling. Collectively, these findings present a novel tumor-suppressive interaction between AIMP2 and Smurf2 and suggest that the disruption of this interaction can lead to oncogenic transformation.-
dc.publisherAmer Assoc Cancer Research-
dc.titleOncogenic mutation of AIMP2/p38 inhibits its tumor-suppresive interaction with Smurf2-
dc.title.alternativeOncogenic mutation of AIMP2/p38 inhibits its tumor-suppresive interaction with Smurf2-
dc.typeArticle-
dc.citation.titleCancer Research-
dc.citation.number11-
dc.citation.endPage3436-
dc.citation.startPage3422-
dc.citation.volume76-
dc.contributor.affiliatedAuthorMyung Hee Kim-
dc.contributor.alternativeName김대규-
dc.contributor.alternativeName이진영-
dc.contributor.alternativeName이지현-
dc.contributor.alternativeName조하연-
dc.contributor.alternativeName강범식-
dc.contributor.alternativeName장송이-
dc.contributor.alternativeName김명희-
dc.contributor.alternativeNameGuo-
dc.contributor.alternativeName한정민-
dc.contributor.alternativeName김성진-
dc.contributor.alternativeName김성훈-
dc.identifier.bibliographicCitationCancer Research, vol. 76, no. 11, pp. 3422-3436-
dc.identifier.doi10.1158/0008-5472.CAN-15-3255-
dc.description.journalClassY-
Appears in Collections:
Division of Biomedical Research > Metabolic Regulation Research Center > 1. Journal Articles
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