PDBsum entry 2mbe

Protein binding

PDB id: 2mbe

Contents

Protein chain

75 a.a.

PDB id:

2mbe

Name:

Protein binding

Title:

Backbone 1h and 15n chemical shift assignments for the first domain of fat10

Structure:

Ubiquitin d. Chain: a. Synonym: diubiquitin, ubiquitin-like protein fat10. Engineered: yes

Source:

Homo sapiens. Human. Organism_taxid: 9606. Gene: ubd, fat10. Expressed in: escherichia coli. Expression_system_taxid: 562.

NMR struc:

8 models

Authors:

W.Wang,L.Lim,H.Qin

Key ref:

S.S.Theng et al. (2014). Disruption of FAT10-MAD2 binding inhibits tumor progression. Proc Natl Acad Sci U S A, 111, E5282. PubMed id: 25422469 DOI: 10.1073/pnas.1403383111

Date:

30-Jul-13 Release date: 27-Aug-14

Protein chain

O15205  (UBD_HUMAN) -  Ubiquitin D from Homo sapiens

Seq: 165 a.a.

Struc: 75 a.a.*

* PDB and UniProt seqs differ at 1 residue position (black cross)

Enzyme reactions

• Enzyme class: E.C.?

DOI no: 10.1073/pnas.1403383111

Proc Natl Acad Sci U S A 111:E5282 (2014)

PubMed id: 25422469

Disruption of FAT10-MAD2 binding inhibits tumor progression.

S.S.Theng, W.Wang, W.C.Mah, C.Chan, J.Zhuo, Y.Gao, H.Qin, L.Lim, S.S.Chong, J.Song, C.G.Lee.

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.