Journal of Biosciences

, Volume 41, Issue 2, pp 295–311 | Cite as

Bromodomain and extra-terminal (BET) family proteins: New therapeutic targets in major diseases

  • Balasundaram PadmanabhanEmail author
  • Shruti Mathur
  • Ramu Manjula
  • Shailesh Tripathi


The bromodomains and extra-terminal domain (BET) family proteins recognize acetylated chromatin through their bromodomains (BDs) and help in regulating gene expression. BDs are chromatin ‘readers’: by interacting with acetylated lysines on the histone tails, they recruit chromatin-regulating proteins on the promoter region to regulate gene expression and repression. Extensive efforts have been employed by scientific communities worldwide to identify and develop potential inhibitors of BET family BDs to regulate protein expression by inhibiting acetylated histone (H3/H4) interactions. Several small molecule inhibitors have been reported, which not only have high affinity but also have high specificity to BET BDs. These developments make BET family proteins an important therapeutic targets for major diseases such as cancer, neurological disorders, obesity and inflammation. Here, we review and discuss the structural biology of BET family BDs and their applications in major diseases.


BET family bromodomains drug targets epigenetics structural biology transcription regulation 

Abbreviations used


acute myeloid leukaemia


B-cell lymphoma 2




bromodomain and extra-terminal


Burkitt’s lymphoma


bromodomain containing protein 2


bromodomain containing protein 3


bromodomain containing protein 4


bromodomain, testis specific


cyclin-dependent kinase


cAMP (adenosine 3′5′ cyclic monophosphate) response element-binding protein


CREB binding protein


epilepsy juvenile myoclonic 1


fluorescence anisotropy


FOS-like antigen 1


fluorescence polarization


fluorescence resonance energy transfer


gamma-aminobutyric acid




histone acetyl transferases


HIV-associated neuropathy


high-throughput screening


idiopathic generalized epilepsy


isothermal calorimetry


juvenile myoclonic epilepsy


acetylated lysine


motif b


lung adenocarcinoma


V-Myc Avian Myelocytomatosis Viral Oncogene Neuroblastoma Derived Homolog


NUT midline carcinoma


nuclear magnetic resonance


nuclear protein in testis


polymerase associated factor complex


positive transcription elongation factor


post-translational modifications




super elongation complex


surface Plasmon resonance


virtual screening



BP is grateful to the Department of Biotechnology (DBT), India, for the financial support (102/IFD/SAN/792/2013-14). SM is grateful to DST for DST WOS-A fellowship (SR/WOS-A/LS-100/2013). MR to CSIR for SRF fellowship (091490(0093) 2012 EMR-1).


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Copyright information

© Indian Academy of Sciences 2016

Authors and Affiliations

  • Balasundaram Padmanabhan
    • 1
    Email author
  • Shruti Mathur
    • 1
  • Ramu Manjula
    • 1
  • Shailesh Tripathi
    • 1
  1. 1.Department of BiophysicsNational Institute of Mental Health and Neurosciences (NIMHANS)BangaloreIndia

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