HUSCAP logo Hokkaido Univ. logo

Hokkaido University Collection of Scholarly and Academic Papers >
Graduate School of Medicine / Faculty of Medicine >
Peer-reviewed Journal Articles, etc >

TRIM40 promotes neddylation of IKKγ and is downregulated in gastrointestinal cancers

Files in This Item:
Car32-7_995-1004.pdf464.3 kBPDFView/Open
Please use this identifier to cite or link to this item:http://hdl.handle.net/2115/49481

Title: TRIM40 promotes neddylation of IKKγ and is downregulated in gastrointestinal cancers
Authors: Noguchi, Keita Browse this author
Okumura, Fumihiko Browse this author
Takahashi, Norihiko Browse this author
Kataoka, Akihiko Browse this author
Kamiyama, Toshiya Browse this author
Todo, Satoru Browse this author →KAKEN DB
Hatakeyama, Shigetsugu Browse this author →KAKEN DB
Keywords: TRIM40
Nedd8
IKKγ
NF-κB
gastrointestinal cancer
Issue Date: Jul-2011
Publisher: Oxford University Press
Journal Title: Carcinogenesis
Volume: 32
Issue: 7
Start Page: 995
End Page: 1004
Publisher DOI: 10.1093/carcin/bgr068
PMID: 21474709
Abstract: Gastrointestinal neoplasia seems to be a common consequence of chronic inflammation in the gastrointestinal epithelium. NF-κB is an important transcription factor for carcinogenesis in chronic inflammatory diseases and plays a key role in promoting inflammation-associated carcinoma in the gastrointestinal tract. Activation of NF-κB is regulated by several posttranslational modifications including phosphorylation, ubiquitination and neddylation. In this study, we showed that TRIM 40 is highly expressed in the gastrointestinal tract and that TRIM40 physically binds to Nedd8, which is conjugated to target proteins by neddylation. We also found that TRIM40 promotes the neddylation of IKKγ, which is a crucial regulator for NF-κB activation, and consequently causes inhibition of NF-κB activity, whereas a dominant-negative mutant of TRIM40 lacking the RING domain does not inhibit NF-κB activity. Knockdown of TRIM40 in the small intestinal epithelial cell line IEC-6 caused NF-κB activation followed by increased cell growth. In addition, we found that TRIM40 is highly expressed in normal gastrointestinal epithelia but that TRIM40 is downregulated in gastrointestinal carcinomas and chronic inflammatory lesions of the gastrointestinal tract. These findings suggest that TRIM40 inhibits NF-κB activity via neddylation of IKKγ and that TRIM40 prevents inflammation-associated carcinogenesis in the gastrointestinal tract.
Rights: This is a pre-copy-editing, author-produced PDF of an article accepted for publication in Carcinogenesis following peer review. The definitive publisher-authenticated version Carcinogenesis (2011) 32(7): 995-1004 is available online at: http://carcin.oxfordjournals.org/content/32/7/995
Type: article (author version)
URI: http://hdl.handle.net/2115/49481
Appears in Collections:医学院・医学研究院 (Graduate School of Medicine / Faculty of Medicine) > 雑誌発表論文等 (Peer-reviewed Journal Articles, etc)

Submitter: 畠山 鎮次

Export metadata:

OAI-PMH ( junii2 , jpcoar )

MathJax is now OFF:


 

Feedback - Hokkaido University