Structural Mechanism of Transcriptional Regulator NSD3 Recognition by the ET Domain of BRD4

Overview

Journal Structure

Publisher Cell Press

Specialties Biochemistry
Biotechnology
Cell Biology
Molecular Biology

Date 2016 Jun 14

PMID 27291650

Citations 35

Authors

Qiang Zhang

Lei Zeng

Chen Shen

Ying Ju

Tsuyoshi Konuma

Chengcheng Zhao

Christopher R Vakoc

Ming-Ming Zhou

Affiliations

Soon will be listed here.

Abstract

The bromodomains and extra-terminal domain (BET) proteins direct gene transcription in chromatin, and represent new drug targets for cancer and inflammation. Here we report that the ET domain of the BET protein BRD4 recognizes an amphipathic protein sequence motif through establishing a two-strand antiparallel β sheet anchored on a hydrophobic cleft of the three-helix bundle. This structural mechanism likely explains BRD4 interactions with numerous cellular and viral proteins such as Kaposi's sarcoma-associated herpesvirus latency-associated nuclear antigen, and NSD3 whose interaction with BRD4 via this ET domain mechanism is essential for acute myeloid leukemia maintenance.

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