 |
PDBsum entry 2mjv
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
 |
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
Transcription
|
PDB id
|
|
|
|
2mjv
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
References listed in PDB file
|
|
|
Key reference
|
|
|
Title
|
|
Disrupting the interaction of brd4 with diacetylated twist suppresses tumorigenesis in basal-Like breast cancer.
|
|
|
Authors
|
|
J.Shi,
Y.Wang,
L.Zeng,
Y.Wu,
J.Deng,
Q.Zhang,
Y.Lin,
J.Li,
T.Kang,
M.Tao,
E.Rusinova,
G.Zhang,
C.Wang,
H.Zhu,
J.Yao,
Y.X.Zeng,
B.M.Evers,
M.M.Zhou,
B.P.Zhou.
|
|
|
Ref.
|
|
Cancer Cell, 2014,
25,
210-225.
[DOI no: ]
|
|
|
PubMed id
|
|
|
|
|
|
Abstract
|
|
|
Twist is a key transcription activator of epithelial-mesenchymal transition
(EMT). It remains unclear how Twist induces gene expression. Here we report a
mechanism by which Twist recruits BRD4 to direct WNT5A expression in basal-like
breast cancer (BLBC). Twist contains a "histone H4-mimic" GK-X-GK
motif that is diacetylated by Tip60. The diacetylated Twist binds the second
bromodomain of BRD4, whose first bromodomain interacts with acetylated H4,
thereby constructing an activated Twist/BRD4/P-TEFb/RNA-Pol II complex at the
WNT5A promoter and enhancer. Pharmacologic inhibition of the Twist-BRD4
association reduced WNT5A expression and suppressed invasion, cancer stem cell
(CSC)-like properties, and tumorigenicity of BLBC cells. Our study indicates
that the interaction with BRD4 is critical for the oncogenic function of Twist
in BLBC.
|
|
|
|
|
|
|
