PDBsum entry 2mjv

Transcription

PDB id: 2mjv

Contents

Protein chains

12 a.a.

128 a.a.

PDB id:

2mjv

Name:

Transcription

Title:

Solution structures of second bromodomain of brd4 with di-acetylated twist peptide

Structure:

Twist-related protein 1. Chain: a. Fragment: peptide (unp residues 68-79). Synonym: class a basic helix-loop-helix protein 38, bhlha38, h-twist. Engineered: yes. Bromodomain-containing protein 4. Chain: b. Fragment: bromodomain 2 (unp residues 333-460). Synonym: brd4, protein hunk1.

Source:

Homo sapiens. Human. Organism_taxid: 9606. Gene: brd4, hunk1

NMR struc:

20 models

Authors:

L.Zeng,M.Zhou

Key ref:

J.Shi et al. (2014). Disrupting the interaction of BRD4 with diacetylated Twist suppresses tumorigenesis in basal-like breast cancer. Cancer Cell, 25, 210-225. PubMed id: 24525235 DOI: 10.1016/j.ccr.2014.01.028

Date:

16-Jan-14 Release date: 19-Mar-14

Protein chain

Q15672  (TWST1_HUMAN) -  Twist-related protein 1 from Homo sapiens

Seq: 202 a.a.

Struc: 12 a.a.*

Protein chain

O60885  (BRD4_HUMAN) -  Bromodomain-containing protein 4 from Homo sapiens

Seq: 1362 a.a.

Struc: 128 a.a.

* PDB and UniProt seqs differ at 2 residue positions (black crosses)

DOI no: 10.1016/j.ccr.2014.01.028

Cancer Cell 25:210-225 (2014)

PubMed id: 24525235

Disrupting the interaction of BRD4 with diacetylated Twist suppresses tumorigenesis in basal-like breast cancer.

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.

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.