HUSCAP logo Hokkaido Univ. logo

Hokkaido University Collection of Scholarly and Academic Papers >
遺伝子病制御研究所  >
雑誌発表論文等  >

Identification of nerve growth factor-responsive element of the TCL1 promoter as a novel negative regulatory element

フルテキスト
JBC281-38.pdf758.58 kBPDF見る/開く
この文献へのリンクには次のURLを使用してください:http://hdl.handle.net/2115/14759

タイトル: Identification of nerve growth factor-responsive element of the TCL1 promoter as a novel negative regulatory element
著者: Hiromura, Makoto 著作を一覧する
Suizu, Futoshi 著作を一覧する
Narita, Masumi 著作を一覧する
Kinowaki, Keiichi 著作を一覧する
Noguchi, Masayuki 著作を一覧する
発行日: 2006年 9月22日
出版者: American Society for Biochemistry and Molecular Biology
誌名: Journal of Biological Chemistry
巻: 281
号: 38
開始ページ: 27753
終了ページ: 27764
出版社 DOI: 10.1074/jbc.M602420200
抄録: The serine/threonine kinase, Akt (protein kinase B) plays a central role in the regulation of intracellular cell survival. Recently, we demonstrated that the proto-oncogene TCL1, overexpressed in human T-cell prolymphocytic leukemia, is an Akt kinase co-activator. Tightly restricted TCL1 gene expression in early developmental cells suggested that the TCL1 gene is regulated at a transcriptional level. To characterize how TCL1 gene expression is regulated, we cloned the 5'-promoter of the TCL1 gene located at human chromosome 14q32. The 5'-TCL1 promoter region contains a TATA box with cis-regulatory elements for Nur77/NGFI-B (nerve growth factor-responsive element (NBRE), CCAAGGTCA), NFB, and fork head transcription factor. Nur77/NGFI-B, an orphan receptor superfamily transcription factor implicated in T-cell apoptosis, is a substrate for Akt. We hypothesized that TCL1 transactivity is regulated through Akt-induced phosphorylation of Nur77/NGFI-B in vivo. In an electrophoretic mobility shift assay with chromosomal immunoprecipitation assays, wild-type Nur77, but not S350A mutant Nur77, could specifically bind to TCL1-NBRE. A luciferase assay demonstrated that TCL1-NBRE is required for inhibition of TCL1 transactivity upon nerve growth factor/platelet-derived growth factor stimulation, which activates Akt and phosphorylates Nur77. Using a chromosomal immunoprecipitation assay with reverse transcription-PCR, nerve growth factor stimulation inhibited binding of endogenous Nur77 to TCL1-NBRE, in turn, suppressing TCL1 gene expression. The results together establish that TCL1-NBRE is a novel negative regulatory element of Nur77 (NGFI-B). To the best of our knowledge, TCL1-NBRE is the first direct target of Nur77 involving the regulation of intracellular cell death survival. This Akt-induced inhibitory mechanism of TCL1 should play an important role in immunological and/or neuronal development in vivo
Rights: Copyright © 2006 by the American Society for Biochemistry and Molecular Biology
Relation (URI): http://www.jpc.org/
資料タイプ: article (author version)
URI: http://hdl.handle.net/2115/14759
出現コレクション:雑誌発表論文等 (Peer-reviewed Journal Articles, etc)

提供者: 野口 昌幸

 

本サイトに関するご意見・お問い合わせは repo at lib.hokudai.ac.jp へお願いします。 - 北海道大学