title: Bromodomain and extra-terminal (BET) family proteins: New therapeutic targets in major diseases.
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.
authors.affiliation: Department of Biophysics, National Institute of Mental Health and Neurosciences (NIMHANS), Bangalore 560 029, India.
authors.forename: Balasundaram
authors.initials: B
authors.lastname: Padmanabhan
authors.forename: Shruti
authors.initials: S
authors.lastname: Mathur
authors.forename: Ramu
authors.initials: R
authors.lastname: Manjula
authors.forename: Shailesh
authors.initials: S
authors.lastname: Tripathi
mesh_terms: D000107:Acetylation; D002843:Chromatin / Q000235:genetics; D005786:Gene Expression Regulation; D006657:Histones / Q000235:genetics; D006801:Humans; D007249:Inflammation / Q000235:genetics* / Q000628:therapy; D005810:Multigene Family; D009369:Neoplasms / Q000235:genetics* / Q000628:therapy; D009419:Nerve Tissue Proteins / Q000235:genetics*; D009422:Nervous System Diseases / Q000235:genetics / Q000628:therapy; D009765:Obesity / Q000235:genetics* / Q000628:therapy; D011956:Receptors, Cell Surface / Q000235:genetics*
chemical_list: D002843:Chromatin; C462501:DNER protein, human; D006657:Histones; D009419:Nerve Tissue Proteins; D011956:Receptors, Cell Surface