2MJV
Solution structures of second bromodomain of Brd4 with di-acetylated Twist peptide
Summary for 2MJV
| Entry DOI | 10.2210/pdb2mjv/pdb |
| NMR Information | BMRB: 19738 |
| Descriptor | Twist-related protein 1, Bromodomain-containing protein 4 (2 entities in total) |
| Functional Keywords | tumorigenesis, transcription |
| Biological source | Homo sapiens (human) More |
| Cellular location | Nucleus: Q15672 O60885 |
| Total number of polymer chains | 2 |
| Total formula weight | 16142.52 |
| Authors | |
| Primary citation | Shi, J.,Wang, Y.,Zeng, L.,Wu, Y.,Deng, J.,Zhang, Q.,Lin, Y.,Li, J.,Kang, T.,Tao, M.,Rusinova, E.,Zhang, G.,Wang, C.,Zhu, H.,Yao, J.,Zeng, Y.X.,Evers, B.M.,Zhou, M.M.,Zhou, B.P. Disrupting the Interaction of BRD4 with Diacetylated Twist Suppresses Tumorigenesis in Basal-like Breast Cancer. Cancer Cell, 25:210-225, 2014 Cited by PubMed 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. PubMed: 24525235DOI: 10.1016/j.ccr.2014.01.028 PDB entries with the same primary citation |
| Experimental method | SOLUTION NMR |
Structure validation
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