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PDBsum entry 2mbe
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Protein binding
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PDB id
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2mbe
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References listed in PDB file
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Key reference
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Title
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Disruption of fat10-Mad2 binding inhibits tumor progression.
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Authors
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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.
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Ref.
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Proc Natl Acad Sci U S A, 2014,
111,
E5282.
[DOI no: ]
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PubMed id
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Abstract
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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.
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