Histone modification enzymes: novel targets for cancer drugs
In eukaryotes, genomic DNA is packaged with histone proteins into the cell nucleus as chromatin, condensing the DNA > 10,000-fold. Chromatin is highly dynamic and exerts profound control on gene expression. Localised chromatin decondensation facilitates access of nuclear machinery. Chromatin disp...
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description | In eukaryotes, genomic DNA is packaged with histone proteins into the cell nucleus as chromatin, condensing the DNA > 10,000-fold. Chromatin is highly dynamic and exerts profound control on gene expression. Localised chromatin decondensation facilitates access of nuclear machinery. Chromatin displays epigenetic inheritance, in that changes in its structure can pass to the next generation independently of the DNA sequence itself. It is now clear that the post-translational modification of histones, for example, acetylation, methylation and phosphorylation, plays a crucial role in the regulation of nuclear function through the 'histone code'. There has been significant progress in identifying and understanding the enzymes that control these complex processes, in particular histone acetyltransferases and histone deacetylases. The exciting discovery that compounds inhibiting histone deacetylase activity also have antitumour properties has focused attention on their use as anticancer drugs. As a consequence, there is ongoing evaluation of several histone deacetylase inhibitor compounds in Phase I and II clinical trials with promising early results. It is likely that many of the enzymes involved in the control of histone modification will provide therapeutic opportunities for the treatment of cancer, including histone methyltransferases and Aurora kinases. |
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Chromatin is highly dynamic and exerts profound control on gene expression. Localised chromatin decondensation facilitates access of nuclear machinery. Chromatin displays epigenetic inheritance, in that changes in its structure can pass to the next generation independently of the DNA sequence itself. It is now clear that the post-translational modification of histones, for example, acetylation, methylation and phosphorylation, plays a crucial role in the regulation of nuclear function through the 'histone code'. There has been significant progress in identifying and understanding the enzymes that control these complex processes, in particular histone acetyltransferases and histone deacetylases. The exciting discovery that compounds inhibiting histone deacetylase activity also have antitumour properties has focused attention on their use as anticancer drugs. As a consequence, there is ongoing evaluation of several histone deacetylase inhibitor compounds in Phase I and II clinical trials with promising early results. 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Chromatin is highly dynamic and exerts profound control on gene expression. Localised chromatin decondensation facilitates access of nuclear machinery. Chromatin displays epigenetic inheritance, in that changes in its structure can pass to the next generation independently of the DNA sequence itself. It is now clear that the post-translational modification of histones, for example, acetylation, methylation and phosphorylation, plays a crucial role in the regulation of nuclear function through the 'histone code'. There has been significant progress in identifying and understanding the enzymes that control these complex processes, in particular histone acetyltransferases and histone deacetylases. The exciting discovery that compounds inhibiting histone deacetylase activity also have antitumour properties has focused attention on their use as anticancer drugs. As a consequence, there is ongoing evaluation of several histone deacetylase inhibitor compounds in Phase I and II clinical trials with promising early results. It is likely that many of the enzymes involved in the control of histone modification will provide therapeutic opportunities for the treatment of cancer, including histone methyltransferases and Aurora kinases.</description><subject>acetylation</subject><subject>Acetylation - drug effects</subject><subject>Acetyltransferases - drug effects</subject><subject>Antineoplastic Agents - classification</subject><subject>Antineoplastic Agents - pharmacology</subject><subject>Antineoplastic Agents - therapeutic use</subject><subject>chromatin</subject><subject>Chromatin - drug effects</subject><subject>Chromatin - metabolism</subject><subject>Clinical Trials as Topic</subject><subject>Drug Design</subject><subject>epigenetics</subject><subject>Gene Expression Regulation, Neoplastic - drug effects</subject><subject>Gene Silencing - drug effects</subject><subject>HAT</subject><subject>HDAC</subject><subject>HDAC inhibitor</subject><subject>histone</subject><subject>Histone Acetyltransferases</subject><subject>Histone Deacetylases - drug effects</subject><subject>Histone-Lysine N-Methyltransferase - drug effects</subject><subject>Histones - chemistry</subject><subject>Histones - metabolism</subject><subject>methylation</subject><subject>Methylation - drug effects</subject><subject>Multicenter Studies as Topic</subject><subject>Neoplasm Proteins - metabolism</subject><subject>Neoplasms - drug therapy</subject><subject>Neoplasms - enzymology</subject><subject>Neoplasms - metabolism</subject><subject>Phosphorylation - drug effects</subject><subject>Protamine Kinase - drug effects</subject><subject>Protein Methyltransferases</subject><subject>Protein Processing, Post-Translational - drug effects</subject><subject>Protein Structure, Tertiary</subject><subject>Protein Tyrosine Phosphatases</subject><issn>1472-8214</issn><issn>1744-7623</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2004</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqFkEtLxDAUhYMovveupCt3HfNOq25k8AWCG12HNLl1OrSNJq0y_nozzIi4UFf3wnlw-BA6InhCBFGnhCtaUMIn5YRMCBMbaJcoznMlKdtMf5Lzpb6D9mKcY0ylUHwb7aSwEITjXXRx28TB95B13jV1Y83Q-D6D_mPRQTzLev8GbTaY8AxDzGofMmt6CyFzYXyOB2irNm2Ew_XdR0_XV4_T2_z-4eZuenmfW8b5kBNKcamosI4qKTlnwKiVBXZOAq0MLSQvFBjFhMO4clXaqChWpgRFWCEE20cnq96X4F9HiIPummihbU0PfoxakZJLqfi_RoqZkgovG_HKaIOPMUCtX0LTmbDQBOslWv2FVpea6IQ2RY7X3WPVgfsOrFkmw_nK0PQJVGfefWidHsyi9aEOCVsTNfuj_uxHegamHWbWBNBzP4Y-8f192yfWmJfr</recordid><startdate>20040501</startdate><enddate>20040501</enddate><creator>Kristeleit, Rebecca</creator><creator>Stimson, Lindsay</creator><creator>Workman, Paul</creator><creator>Aherne, Wynne</creator><general>Ashley Publications Ltd</general><general>Taylor & Francis</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>7QO</scope><scope>7TM</scope><scope>8FD</scope><scope>FR3</scope><scope>P64</scope><scope>RC3</scope><scope>7X8</scope></search><sort><creationdate>20040501</creationdate><title>Histone modification enzymes: novel targets for cancer drugs</title><author>Kristeleit, Rebecca ; Stimson, Lindsay ; Workman, Paul ; Aherne, Wynne</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c344t-12209725cd2766443e32c680dd6e2ba286487ea735d00bdb5747207a9e7138553</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2004</creationdate><topic>acetylation</topic><topic>Acetylation - drug effects</topic><topic>Acetyltransferases - drug effects</topic><topic>Antineoplastic Agents - classification</topic><topic>Antineoplastic Agents - pharmacology</topic><topic>Antineoplastic Agents - therapeutic use</topic><topic>chromatin</topic><topic>Chromatin - drug effects</topic><topic>Chromatin - metabolism</topic><topic>Clinical Trials as Topic</topic><topic>Drug Design</topic><topic>epigenetics</topic><topic>Gene Expression Regulation, Neoplastic - drug effects</topic><topic>Gene Silencing - drug effects</topic><topic>HAT</topic><topic>HDAC</topic><topic>HDAC inhibitor</topic><topic>histone</topic><topic>Histone Acetyltransferases</topic><topic>Histone Deacetylases - drug effects</topic><topic>Histone-Lysine N-Methyltransferase - drug effects</topic><topic>Histones - chemistry</topic><topic>Histones - metabolism</topic><topic>methylation</topic><topic>Methylation - drug effects</topic><topic>Multicenter Studies as Topic</topic><topic>Neoplasm Proteins - metabolism</topic><topic>Neoplasms - drug therapy</topic><topic>Neoplasms - enzymology</topic><topic>Neoplasms - metabolism</topic><topic>Phosphorylation - drug effects</topic><topic>Protamine Kinase - drug effects</topic><topic>Protein Methyltransferases</topic><topic>Protein Processing, Post-Translational - drug effects</topic><topic>Protein Structure, Tertiary</topic><topic>Protein Tyrosine Phosphatases</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Kristeleit, Rebecca</creatorcontrib><creatorcontrib>Stimson, Lindsay</creatorcontrib><creatorcontrib>Workman, Paul</creatorcontrib><creatorcontrib>Aherne, Wynne</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Biotechnology Research Abstracts</collection><collection>Nucleic Acids Abstracts</collection><collection>Technology Research Database</collection><collection>Engineering Research Database</collection><collection>Biotechnology and BioEngineering Abstracts</collection><collection>Genetics Abstracts</collection><collection>MEDLINE - Academic</collection><jtitle>Expert opinion on emerging drugs</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Kristeleit, Rebecca</au><au>Stimson, Lindsay</au><au>Workman, Paul</au><au>Aherne, Wynne</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Histone modification enzymes: novel targets for cancer drugs</atitle><jtitle>Expert opinion on emerging drugs</jtitle><addtitle>Expert Opin Emerg Drugs</addtitle><date>2004-05-01</date><risdate>2004</risdate><volume>9</volume><issue>1</issue><spage>135</spage><epage>154</epage><pages>135-154</pages><issn>1472-8214</issn><eissn>1744-7623</eissn><abstract>In eukaryotes, genomic DNA is packaged with histone proteins into the cell nucleus as chromatin, condensing the DNA > 10,000-fold. Chromatin is highly dynamic and exerts profound control on gene expression. Localised chromatin decondensation facilitates access of nuclear machinery. Chromatin displays epigenetic inheritance, in that changes in its structure can pass to the next generation independently of the DNA sequence itself. It is now clear that the post-translational modification of histones, for example, acetylation, methylation and phosphorylation, plays a crucial role in the regulation of nuclear function through the 'histone code'. There has been significant progress in identifying and understanding the enzymes that control these complex processes, in particular histone acetyltransferases and histone deacetylases. The exciting discovery that compounds inhibiting histone deacetylase activity also have antitumour properties has focused attention on their use as anticancer drugs. 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subjects | acetylation Acetylation - drug effects Acetyltransferases - drug effects Antineoplastic Agents - classification Antineoplastic Agents - pharmacology Antineoplastic Agents - therapeutic use chromatin Chromatin - drug effects Chromatin - metabolism Clinical Trials as Topic Drug Design epigenetics Gene Expression Regulation, Neoplastic - drug effects Gene Silencing - drug effects HAT HDAC HDAC inhibitor histone Histone Acetyltransferases Histone Deacetylases - drug effects Histone-Lysine N-Methyltransferase - drug effects Histones - chemistry Histones - metabolism methylation Methylation - drug effects Multicenter Studies as Topic Neoplasm Proteins - metabolism Neoplasms - drug therapy Neoplasms - enzymology Neoplasms - metabolism Phosphorylation - drug effects Protamine Kinase - drug effects Protein Methyltransferases Protein Processing, Post-Translational - drug effects Protein Structure, Tertiary Protein Tyrosine Phosphatases |
title | Histone modification enzymes: novel targets for cancer drugs |
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