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The Bromodomain and Extra-Terminal Domain (BET) Family: Functional Anatomy of BET Paralogous Proteins
The Bromodomain and Extra-Terminal Domain (BET) family of proteins is characterized by the presence of two tandem bromodomains and an extra-terminal domain. The mammalian BET family of proteins comprises BRD2, BRD3, BRD4, and BRDT, which are encoded by paralogous genes that may have been generated b...
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| Published in: | International journal of molecular sciences 2016-11, Vol.17 (11), p.1849-1849 |
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| description | The Bromodomain and Extra-Terminal Domain (BET) family of proteins is characterized by the presence of two tandem bromodomains and an extra-terminal domain. The mammalian BET family of proteins comprises BRD2, BRD3, BRD4, and BRDT, which are encoded by paralogous genes that may have been generated by repeated duplication of an ancestral gene during evolution. Bromodomains that can specifically bind acetylated lysine residues in histones serve as chromatin-targeting modules that decipher the histone acetylation code. BET proteins play a crucial role in regulating gene transcription through epigenetic interactions between bromodomains and acetylated histones during cellular proliferation and differentiation processes. On the other hand, BET proteins have been reported to mediate latent viral infection in host cells and be involved in oncogenesis. Human BRD4 is involved in multiple processes of the DNA virus life cycle, including viral replication, genome maintenance, and gene transcription through interaction with viral proteins. Aberrant BRD4 expression contributes to carcinogenesis by mediating hyperacetylation of the chromatin containing the cell proliferation-promoting genes. BET bromodomain blockade using small-molecule inhibitors gives rise to selective repression of the transcriptional network driven by c-MYC These inhibitors are expected to be potential therapeutic drugs for a wide range of cancers. This review presents an overview of the basic roles of BET proteins and highlights the pathological functions of BET and the recent developments in cancer therapy targeting BET proteins in animal models. |
| doi_str_mv | 10.3390/ijms17111849 |
| format | article |
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The mammalian BET family of proteins comprises BRD2, BRD3, BRD4, and BRDT, which are encoded by paralogous genes that may have been generated by repeated duplication of an ancestral gene during evolution. Bromodomains that can specifically bind acetylated lysine residues in histones serve as chromatin-targeting modules that decipher the histone acetylation code. BET proteins play a crucial role in regulating gene transcription through epigenetic interactions between bromodomains and acetylated histones during cellular proliferation and differentiation processes. On the other hand, BET proteins have been reported to mediate latent viral infection in host cells and be involved in oncogenesis. Human BRD4 is involved in multiple processes of the DNA virus life cycle, including viral replication, genome maintenance, and gene transcription through interaction with viral proteins. Aberrant BRD4 expression contributes to carcinogenesis by mediating hyperacetylation of the chromatin containing the cell proliferation-promoting genes. BET bromodomain blockade using small-molecule inhibitors gives rise to selective repression of the transcriptional network driven by c-MYC These inhibitors are expected to be potential therapeutic drugs for a wide range of cancers. 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The mammalian BET family of proteins comprises BRD2, BRD3, BRD4, and BRDT, which are encoded by paralogous genes that may have been generated by repeated duplication of an ancestral gene during evolution. Bromodomains that can specifically bind acetylated lysine residues in histones serve as chromatin-targeting modules that decipher the histone acetylation code. BET proteins play a crucial role in regulating gene transcription through epigenetic interactions between bromodomains and acetylated histones during cellular proliferation and differentiation processes. On the other hand, BET proteins have been reported to mediate latent viral infection in host cells and be involved in oncogenesis. Human BRD4 is involved in multiple processes of the DNA virus life cycle, including viral replication, genome maintenance, and gene transcription through interaction with viral proteins. Aberrant BRD4 expression contributes to carcinogenesis by mediating hyperacetylation of the chromatin containing the cell proliferation-promoting genes. BET bromodomain blockade using small-molecule inhibitors gives rise to selective repression of the transcriptional network driven by c-MYC These inhibitors are expected to be potential therapeutic drugs for a wide range of cancers. This review presents an overview of the basic roles of BET proteins and highlights the pathological functions of BET and the recent developments in cancer therapy targeting BET proteins in animal models.</description><subject>Animals</subject><subject>Antineoplastic Agents - therapeutic use</subject><subject>BET inhibitor</subject><subject>bromodomain</subject><subject>Bromodomain and Extra-Terminal Domain (BET)</subject><subject>Cell Proliferation - drug effects</subject><subject>Chromatin - drug effects</subject><subject>Chromatin - metabolism</subject><subject>Chromatin - ultrastructure</subject><subject>Epigenesis, Genetic</subject><subject>Evolution, Molecular</subject><subject>Gene Duplication</subject><subject>gene transcription</subject><subject>Genes</subject><subject>histone acetylation</subject><subject>Histones - genetics</subject><subject>Histones - metabolism</subject><subject>Humans</subject><subject>Lysine - metabolism</subject><subject>Multigene Family</subject><subject>Neoplasms - drug therapy</subject><subject>Neoplasms - genetics</subject><subject>Neoplasms - metabolism</subject><subject>Neoplasms - pathology</subject><subject>Oncology</subject><subject>Protein Domains</subject><subject>Protein Isoforms - antagonists & inhibitors</subject><subject>Protein Isoforms - genetics</subject><subject>Protein Isoforms - metabolism</subject><subject>Protein-Serine-Threonine Kinases - antagonists & inhibitors</subject><subject>Protein-Serine-Threonine Kinases - genetics</subject><subject>Protein-Serine-Threonine Kinases - metabolism</subject><subject>Proteins</subject><subject>Review</subject><subject>Signal Transduction</subject><subject>Transcription factors</subject><subject>Virus Diseases - drug therapy</subject><subject>Virus Diseases - genetics</subject><subject>Virus Diseases - metabolism</subject><subject>Virus Diseases - virology</subject><issn>1422-0067</issn><issn>1661-6596</issn><issn>1422-0067</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2016</creationdate><recordtype>article</recordtype><sourceid>PIMPY</sourceid><sourceid>DOA</sourceid><recordid>eNqNks1rFDEYhwdRbK3ePEvASwVHk0kySTwIbd3VQsEe1nN4Jx_bLDOTNpkR978369ay9eQpIb-Hh7wfVfWa4A-UKvwxbIZMBCFEMvWkOiasaWqMW_H04H5Uvch5g3FDG66eV0eNkI1Qqj2u3OrGofMUh2jjAGFEMFq0-DUlqFcuDWGEHn3ZJ6fni9U7tIQh9NtPaDmPZgpxl5-NMMVhi6JHBUHXkKCP6zhndJ3i5MKYX1bPPPTZvbo_T6ofy8Xq4lt99f3r5cXZVW24EFPNwWDDPetcJ3zbKtZ5KyT1nWBAMfOOWilI65Qt9QovMQHKhbWWKQALjJ5Ul3uvjbDRtykMkLY6QtB_HmJaa0hTML3TQLxpWyapcILZzsnGME-d4MA94c3O9Xnvup27wVnjxtKU_pH0cTKGG72OPzUnlJZZFMHpvSDFu9nlSQ8hG9f3MLrSHE0kV0xgIv4HpYo0EmNZ0Lf_oJs4pzKGHcUU47wlpFDv95RJMefk_MO_Cda7tdGHa1PwN4e1PsB_94T-Bp7NvYs</recordid><startdate>20161107</startdate><enddate>20161107</enddate><creator>Taniguchi, Yasushi</creator><general>MDPI AG</general><general>MDPI</general><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>3V.</scope><scope>7X7</scope><scope>7XB</scope><scope>88E</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>8G5</scope><scope>ABUWG</scope><scope>AFKRA</scope><scope>AZQEC</scope><scope>BENPR</scope><scope>CCPQU</scope><scope>DWQXO</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>GNUQQ</scope><scope>GUQSH</scope><scope>K9.</scope><scope>M0S</scope><scope>M1P</scope><scope>M2O</scope><scope>MBDVC</scope><scope>PIMPY</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PRINS</scope><scope>Q9U</scope><scope>7X8</scope><scope>7TK</scope><scope>5PM</scope><scope>DOA</scope><orcidid>https://orcid.org/0000-0001-7837-1598</orcidid></search><sort><creationdate>20161107</creationdate><title>The Bromodomain and Extra-Terminal Domain (BET) Family: Functional Anatomy of BET Paralogous Proteins</title><author>Taniguchi, Yasushi</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c577t-5ac0c5f4beb7f6694bfd783fb74a304fe3d8716e9d7117f801a357ddd49aada43</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2016</creationdate><topic>Animals</topic><topic>Antineoplastic Agents - therapeutic use</topic><topic>BET inhibitor</topic><topic>bromodomain</topic><topic>Bromodomain and Extra-Terminal Domain (BET)</topic><topic>Cell Proliferation - drug effects</topic><topic>Chromatin - drug effects</topic><topic>Chromatin - metabolism</topic><topic>Chromatin - ultrastructure</topic><topic>Epigenesis, Genetic</topic><topic>Evolution, Molecular</topic><topic>Gene Duplication</topic><topic>gene transcription</topic><topic>Genes</topic><topic>histone acetylation</topic><topic>Histones - genetics</topic><topic>Histones - metabolism</topic><topic>Humans</topic><topic>Lysine - metabolism</topic><topic>Multigene Family</topic><topic>Neoplasms - drug therapy</topic><topic>Neoplasms - genetics</topic><topic>Neoplasms - metabolism</topic><topic>Neoplasms - pathology</topic><topic>Oncology</topic><topic>Protein Domains</topic><topic>Protein Isoforms - antagonists & inhibitors</topic><topic>Protein Isoforms - genetics</topic><topic>Protein Isoforms - metabolism</topic><topic>Protein-Serine-Threonine Kinases - antagonists & inhibitors</topic><topic>Protein-Serine-Threonine Kinases - genetics</topic><topic>Protein-Serine-Threonine Kinases - metabolism</topic><topic>Proteins</topic><topic>Review</topic><topic>Signal Transduction</topic><topic>Transcription factors</topic><topic>Virus Diseases - drug therapy</topic><topic>Virus Diseases - genetics</topic><topic>Virus Diseases - metabolism</topic><topic>Virus Diseases - virology</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Taniguchi, Yasushi</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>ProQuest Central (Corporate)</collection><collection>ProQuest_Health & Medical Collection</collection><collection>ProQuest Central (purchase pre-March 2016)</collection><collection>Medical Database (Alumni Edition)</collection><collection>Hospital Premium Collection</collection><collection>Hospital Premium Collection (Alumni Edition)</collection><collection>ProQuest Central (Alumni) (purchase pre-March 2016)</collection><collection>Research Library (Alumni Edition)</collection><collection>ProQuest Central (Alumni)</collection><collection>ProQuest Central</collection><collection>ProQuest Central Essentials</collection><collection>ProQuest Central</collection><collection>ProQuest One Community College</collection><collection>ProQuest Central</collection><collection>Health Research Premium Collection</collection><collection>Health Research Premium Collection (Alumni)</collection><collection>ProQuest Central Student</collection><collection>Research Library Prep</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>Health & Medical Collection (Alumni Edition)</collection><collection>PML(ProQuest Medical Library)</collection><collection>ProQuest_Research Library</collection><collection>Research Library (Corporate)</collection><collection>Publicly Available Content Database</collection><collection>ProQuest One Academic Eastern Edition (DO NOT USE)</collection><collection>ProQuest One Academic</collection><collection>ProQuest One Academic UKI Edition</collection><collection>ProQuest Central China</collection><collection>ProQuest Central Basic</collection><collection>MEDLINE - Academic</collection><collection>Neurosciences Abstracts</collection><collection>PubMed Central (Full Participant titles)</collection><collection>DOAJ Directory of Open Access Journals</collection><jtitle>International journal of molecular sciences</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Taniguchi, Yasushi</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>The Bromodomain and Extra-Terminal Domain (BET) Family: Functional Anatomy of BET Paralogous Proteins</atitle><jtitle>International journal of molecular sciences</jtitle><addtitle>Int J Mol Sci</addtitle><date>2016-11-07</date><risdate>2016</risdate><volume>17</volume><issue>11</issue><spage>1849</spage><epage>1849</epage><pages>1849-1849</pages><issn>1422-0067</issn><issn>1661-6596</issn><eissn>1422-0067</eissn><abstract>The Bromodomain and Extra-Terminal Domain (BET) family of proteins is characterized by the presence of two tandem bromodomains and an extra-terminal domain. The mammalian BET family of proteins comprises BRD2, BRD3, BRD4, and BRDT, which are encoded by paralogous genes that may have been generated by repeated duplication of an ancestral gene during evolution. Bromodomains that can specifically bind acetylated lysine residues in histones serve as chromatin-targeting modules that decipher the histone acetylation code. BET proteins play a crucial role in regulating gene transcription through epigenetic interactions between bromodomains and acetylated histones during cellular proliferation and differentiation processes. On the other hand, BET proteins have been reported to mediate latent viral infection in host cells and be involved in oncogenesis. Human BRD4 is involved in multiple processes of the DNA virus life cycle, including viral replication, genome maintenance, and gene transcription through interaction with viral proteins. Aberrant BRD4 expression contributes to carcinogenesis by mediating hyperacetylation of the chromatin containing the cell proliferation-promoting genes. BET bromodomain blockade using small-molecule inhibitors gives rise to selective repression of the transcriptional network driven by c-MYC These inhibitors are expected to be potential therapeutic drugs for a wide range of cancers. This review presents an overview of the basic roles of BET proteins and highlights the pathological functions of BET and the recent developments in cancer therapy targeting BET proteins in animal models.</abstract><cop>Switzerland</cop><pub>MDPI AG</pub><pmid>27827996</pmid><doi>10.3390/ijms17111849</doi><tpages>1</tpages><orcidid>https://orcid.org/0000-0001-7837-1598</orcidid><oa>free_for_read</oa></addata></record> |
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| subjects | Animals Antineoplastic Agents - therapeutic use BET inhibitor bromodomain Bromodomain and Extra-Terminal Domain (BET) Cell Proliferation - drug effects Chromatin - drug effects Chromatin - metabolism Chromatin - ultrastructure Epigenesis, Genetic Evolution, Molecular Gene Duplication gene transcription Genes histone acetylation Histones - genetics Histones - metabolism Humans Lysine - metabolism Multigene Family Neoplasms - drug therapy Neoplasms - genetics Neoplasms - metabolism Neoplasms - pathology Oncology Protein Domains Protein Isoforms - antagonists & inhibitors Protein Isoforms - genetics Protein Isoforms - metabolism Protein-Serine-Threonine Kinases - antagonists & inhibitors Protein-Serine-Threonine Kinases - genetics Protein-Serine-Threonine Kinases - metabolism Proteins Review Signal Transduction Transcription factors Virus Diseases - drug therapy Virus Diseases - genetics Virus Diseases - metabolism Virus Diseases - virology |
| title | The Bromodomain and Extra-Terminal Domain (BET) Family: Functional Anatomy of BET Paralogous Proteins |
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