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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
Review

Abstract

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.

Keywords

BET family bromodomains drug targets epigenetics structural biology transcription regulation 

Abbreviations used

AML

acute myeloid leukaemia

Bcl2

B-cell lymphoma 2

BD

bromodomain

BET

bromodomain and extra-terminal

BL

Burkitt’s lymphoma

BRD2

bromodomain containing protein 2

BRD3

bromodomain containing protein 3

BRD4

bromodomain containing protein 4

BRDT

bromodomain, testis specific

CDK

cyclin-dependent kinase

CREBP

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

CREBBP

CREB binding protein

EJM1

epilepsy juvenile myoclonic 1

FA

fluorescence anisotropy

FOSL1

FOS-like antigen 1

FP

fluorescence polarization

FRET

fluorescence resonance energy transfer

GABA

gamma-aminobutyric acid

GHB

γ-hydroxybutyrate

HAT

histone acetyl transferases

HIVAN

HIV-associated neuropathy

HTS

high-throughput screening

IGE

idiopathic generalized epilepsy

ITC

isothermal calorimetry

JME

juvenile myoclonic epilepsy

Kac

acetylated lysine

mB

motif b

LAC

lung adenocarcinoma

MYCN

V-Myc Avian Myelocytomatosis Viral Oncogene Neuroblastoma Derived Homolog

NMC

NUT midline carcinoma

NMR

nuclear magnetic resonance

NUT

nuclear protein in testis

PAFc

polymerase associated factor complex

P-TEFb

positive transcription elongation factor

PTM

post-translational modifications

Ptn

Pleotrophin

SEC

super elongation complex

SPR

surface Plasmon resonance

VS

virtual screening

Notes

Acknowledgements

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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