演題詳細

一般口演 / Oral Session

一般口演 18 (Oral Session 18) :エピジェネティクス

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日程
2013年10月11日(金)
時間
15:25 - 16:25
会場
第3会場 / Room No.3 (さっぽろ芸文館 3F 蓬莱)
座長・司会
瀧原 義宏 (Yoshihiro Takihara):1
1:広島大学原爆放射線医科学研究所 幹細胞機能学研究分野
 
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TET2 binds and regulates O-linked N-acetylglucosamine transferase

演題番号 : OS-1-93

榎並 輝和 (Terukazu Enami):1、坂田(柳元) 麻実子 (Mamiko Sakata-Yanagimoto):1、浅部 幸紹 (Yukitsugu Asabe):1、三宅 康行 (Yasuyuki Miyake):1、世良田 聡 (Satoshi Serada):2、仲 哲治 (Tetsuji Naka):2、武藤 秀治 (Hideharu Muto):1、錦井 秀和 (Hidekazu Nishikii):1、横山 泰久 (Yasuhisa Yokoyama):1、小原 直 (Naoshi Obara):1、鈴川 和己 (Kazumi Suzukawa):1、千葉 滋 (Shigeru Chiba):1

1:Department of Hematology, Faculty of Medicine, University of Tsukuba, Japan、2:Laboratory for Immune Signal, National Institute of Biomedical Innovation, Japan

 

[Background]Loss-of-function mutations of TET2 gene have been recently described in various human myeloid and lymphoid malignancies. TET family proteins are considered to regulate gene transcription by converting 5-methylcytosine to 5-hydroxymethylcytosine (5-hmC). However, the downstream mechanism of impairment of TET2 in tumorigenesis still remains unclear.
[Aim]To investigate the TET2 function in detail, we searched for binding partners of TET2.
[Method]Binding proteins of TET2 were explored via mass spectrometry. Binding sites were identified by immunoprecipitation using deletion-mutants. 5-hmC levels in genomic DNA were determined by a dot blot analysis.
[Result]The mass spectrometry analysis identified O-linked N-acetylglucosamine (O-GlcNAc) transferase (OGT) as a TET2-binding partner. OGT is a highly conserved enzyme that catalyzes O-GlcNAc to Ser/Thr residues of substrate proteins. Using deletion-mutants of TET2 and OGT, we found that the C-terminal catalytic domain of TET2 interacts with the N-terminal tetratricopeptide repeat domain of OGT. We next evaluated whether this interaction has impact on enzymatic activity of each protein. Although O-GlcNAcylation of TET2 was observed in cells transfected with OGT, global 5-hmC levels were not affected. In contrast, Global protein GlcNAcylation detected by immunoblot analysis was reduced in TET2-knockdown cells.
[Conclusion]These results reveal that enzymatic activity of OGT is dependent on TET2. Now we are further working on the involvement of interaction of OGT and TET2 in pathogenesis of hematologic malignancies.

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