Enigma negatively regulates p53 through MDM2 and promotes tumor cell survival in mice

Cited 44 time in scopus
Metadata Downloads

Full metadata record

DC FieldValueLanguage
dc.contributor.authorCho-Rok Jung-
dc.contributor.authorJung Hwa Lim-
dc.contributor.authorY Choi-
dc.contributor.authorD G Kim-
dc.contributor.authorK J Kang-
dc.contributor.authorS M Noh-
dc.contributor.authorDong Soo Im-
dc.date.accessioned2017-04-19T09:20:50Z-
dc.date.available2017-04-19T09:20:50Z-
dc.date.issued2010-
dc.identifier.issn0021-9738-
dc.identifier.uri10.1172/JCI42674ko
dc.identifier.urihttps://oak.kribb.re.kr/handle/201005/9867-
dc.description.abstractThe human E3 ubiquitin ligase murine double minute 2 (MDM2) targets the tumor suppressor p53 for ubiquitination and degradation but also promotes its own ubiquitination and subsequent degradation. As the balance between MDM2 and p53 levels plays a crucial role in regulating cell proliferation and apoptosis, we sought to identify factors selectively inhibiting MDM2 self-ubiquitination. Here we have shown that the LIM domain protein Enigma directly interacts with MDM2 to form a ternary complex with p53 in vitro and in human hepatoma and colon carcinoma cell lines and mouse embryonic fibroblasts. We found that Enigma elicited p53 degradation by inhibiting MDM2 self-ubiquitination and increasing its ubiquitin ligase activity toward p53 in cells. Moreover, mitogenic stimuli such as serum, FGF, and HGF increased Enigma transcription via induction of serum response factor (SRF), leading to MDM2 stabilization and subsequent p53 degradation. We observed similar results in the livers of mice treated with HGF. In humans, we found SRF and Enigma coexpressed with MDM2 but not p53 in several liver and stomach tumors. Finally, we showed that Enigma promoted cell survival and chemoresistance by suppressing p53-mediated apoptosis in both cell lines and a mouse xenograft model. Our findings suggest a role for Enigma in tumorigenesis and uncover a mechanism whereby mitogens attenuate p53 antiproliferative activity through an SRF/Enigma/MDM2 pathway.-
dc.publisherAmer Soc Clinical Investigation Inc-
dc.titleEnigma negatively regulates p53 through MDM2 and promotes tumor cell survival in mice-
dc.title.alternativeEnigma negatively regulates p53 through MDM2 and promotes tumor cell survival in mice-
dc.typeArticle-
dc.citation.titleJournal of Clinical Investigation-
dc.citation.number12-
dc.citation.endPage4506-
dc.citation.startPage4493-
dc.citation.volume120-
dc.contributor.affiliatedAuthorCho-Rok Jung-
dc.contributor.affiliatedAuthorJung Hwa Lim-
dc.contributor.affiliatedAuthorDong Soo Im-
dc.contributor.alternativeName정초록-
dc.contributor.alternativeName임정화-
dc.contributor.alternativeName최윤정-
dc.contributor.alternativeName김대곤-
dc.contributor.alternativeName강구정-
dc.contributor.alternativeName노승무-
dc.contributor.alternativeName임동수-
dc.identifier.bibliographicCitationJournal of Clinical Investigation, vol. 120, no. 12, pp. 4493-4506-
dc.identifier.doi10.1172/JCI42674-
dc.description.journalClassY-
Appears in Collections:
Division of Research on National Challenges > Stem Cell Convergenece Research Center > 1. Journal Articles
Files in This Item:

Items in OpenAccess@KRIBB are protected by copyright, with all rights reserved, unless otherwise indicated.