2MBE

Backbone 1H and 15N Chemical Shift Assignments for the first domain of FAT10

2MBE の概要

• エントリーDOI: 10.2210/pdb2mbe/pdb
• NMR情報: BMRB: 19397
• 分子名称: Ubiquitin D (1 entity in total)
• 機能のキーワード: fat10, protein binding
• 由来する生物種: Homo sapiens (human)
• 細胞内の位置: Nucleus : O15205
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 8676.23

構造登録者

Wang, W.,Lim, L.,Qin, H. (登録日: 2013-07-30, 公開日: 2014-08-27, 最終更新日: 2024-05-15)

主引用文献

Theng, S.S.,Wang, W.,Mah, W.C.,Chan, C.,Zhuo, J.,Gao, Y.,Qin, H.,Lim, L.,Chong, S.S.,Song, J.,Lee, C.G.
Disruption of FAT10-MAD2 binding inhibits tumor progression.
Proc.Natl.Acad.Sci.USA, 111:E5282-E5291, 2014

PubMed Abstract: FAT10 (HLA-F-adjacent transcript 10) is a ubiquitin-like modifier that is commonly overexpressed in various tumors. It was found to play a role in mitotic regulation through its interaction with mitotic arrest-deficient 2 (MAD2). Overexpression of FAT10 promotes tumor growth and malignancy. Here, we identified the MAD2-binding interface of FAT10 to be located on its first ubiquitin-like domain whose NMR structure thus was determined. We further proceeded to demonstrate that disruption of the FAT10-MAD2 interaction through mutation of specific MAD2-binding residues did not interfere with the interaction of FAT10 with its other known interacting partners. Significantly, ablation of the FAT10-MAD2 interaction dramatically limited the promalignant capacity of FAT10, including promoting tumor growth in vivo and inducing aneuploidy, proliferation, migration, invasion, and resistance to apoptosis in vitro. Our results strongly suggest that the interaction of FAT10 with MAD2 is a key mechanism underlying the promalignant property of FAT10 and offer prospects for the development of anticancer strategies.

PubMed: 25422469
DOI: 10.1073/pnas.1403383111

実験手法

SOLUTION NMR