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Regulation of human apolipoprotein B gene expression at multiple levels
Apolipoprotein B is a large, amphipathic protein that plays a central role in lipoprotein metabolism. Because its overproduction and deficiency leads to metabolic and pathologic disorders, much effort has been paid to investigate the mechanisms of how its homeostasis is achieved. Earlier and recent...
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Published in: | Experimental Cell Research 2003-10, Vol.290 (1), p.1-12 |
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description | Apolipoprotein B is a large, amphipathic protein that plays a central role in lipoprotein metabolism. Because its overproduction and deficiency leads to metabolic and pathologic disorders, much effort has been paid to investigate the mechanisms of how its homeostasis is achieved. Earlier and recent studies have showed that apoB gene locus might reside in different chromatin domains in the hepatic and intestinal cells, and two sets of very distinct regulatory elements operate to control its transcription. Posttranscriptional modification of apoB mRNA is performed by a multicomponent enzyme complex, several possible pathways regulate the editing efficiency. Understanding of the mechanism responsible for apoB mRNA editing will provide the basis for C-to-U editing in gene therapy. In addition to apoB mRNA abundance and stability, its translation can be also regulated at the steps of elongation. The translocation of apoB into the ER is an important and complicated process that is less understood. Successful transport and correct folding of apoB may lead to its final secretion, otherwise subject to intracellular degradation, which is accomplished by proteasomal and nonproteasomal pathways at multiple levels and may differ among cell types. |
doi_str_mv | 10.1016/S0014-4827(03)00313-6 |
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Because its overproduction and deficiency leads to metabolic and pathologic disorders, much effort has been paid to investigate the mechanisms of how its homeostasis is achieved. Earlier and recent studies have showed that apoB gene locus might reside in different chromatin domains in the hepatic and intestinal cells, and two sets of very distinct regulatory elements operate to control its transcription. Posttranscriptional modification of apoB mRNA is performed by a multicomponent enzyme complex, several possible pathways regulate the editing efficiency. Understanding of the mechanism responsible for apoB mRNA editing will provide the basis for C-to-U editing in gene therapy. In addition to apoB mRNA abundance and stability, its translation can be also regulated at the steps of elongation. The translocation of apoB into the ER is an important and complicated process that is less understood. Successful transport and correct folding of apoB may lead to its final secretion, otherwise subject to intracellular degradation, which is accomplished by proteasomal and nonproteasomal pathways at multiple levels and may differ among cell types.</description><subject>Animals</subject><subject>Apolipoprotein B</subject><subject>Apolipoproteins B - biosynthesis</subject><subject>Apolipoproteins B - genetics</subject><subject>Apolipoproteins B - metabolism</subject><subject>Degradation</subject><subject>Gene Expression Regulation - genetics</subject><subject>Gene transcription</subject><subject>Humans</subject><subject>Intestinal Mucosa - metabolism</subject><subject>Intestines - cytology</subject><subject>Liver - cytology</subject><subject>Liver - metabolism</subject><subject>mRNA editing</subject><subject>Protein Biosynthesis - genetics</subject><subject>Protein Transport - genetics</subject><subject>RNA Editing - genetics</subject><subject>RNA, Messenger - genetics</subject><subject>RNA, Messenger - metabolism</subject><subject>Translation</subject><subject>Translocation</subject><issn>0014-4827</issn><issn>1090-2422</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2003</creationdate><recordtype>article</recordtype><recordid>eNqFkMtKxTAQhoMoerw8gtKV6KI6k6RJuxI9eANB8LIOaTvnGEkvNq3o29tzQZeuBobvn3_4GDtEOENAdf4MgDKWKdcnIE4BBIpYbbAJQgYxl5xvsskvssN2Q3gHgDRFtc12UCaodCom7PaJ5oO3vWvqqJlFb0Nl68i2jXdt03ZNT66OrqI51RTRV9tRCAvS9lE1-N61niJPn-TDPtuaWR_oYD332OvN9cv0Ln54vL2fXj7Ehch4H6PCQifccsxQg5JJmpYpJJkoM52XpNFqm5VC2plVUua61ErnWOQiRzvuSOyx49Xd8bmPgUJvKhcK8t7W1AzB6ESjVkr_C6JOEwmcj2CyAouuCaGjmWk7V9nu2yCYhWqzVG0WHg0Is1Rt1Jg7WhcMeUXlX2rtdgQuVsCohz4ddSYUjuqCStdR0Zuycf9U_ACvzY2T</recordid><startdate>20031015</startdate><enddate>20031015</enddate><creator>Wang, Ai-Bing</creator><creator>Liu, De-Pei</creator><creator>Liang, Chih-Chuan</creator><general>Elsevier Inc</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>7TM</scope><scope>7X8</scope></search><sort><creationdate>20031015</creationdate><title>Regulation of human apolipoprotein B gene expression at multiple levels</title><author>Wang, Ai-Bing ; Liu, De-Pei ; Liang, Chih-Chuan</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c392t-161c752a21917064588d80593d97bde71a7a9d34afa644b7d767b1cb3b1aafae3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2003</creationdate><topic>Animals</topic><topic>Apolipoprotein B</topic><topic>Apolipoproteins B - biosynthesis</topic><topic>Apolipoproteins B - genetics</topic><topic>Apolipoproteins B - metabolism</topic><topic>Degradation</topic><topic>Gene Expression Regulation - genetics</topic><topic>Gene transcription</topic><topic>Humans</topic><topic>Intestinal Mucosa - metabolism</topic><topic>Intestines - cytology</topic><topic>Liver - cytology</topic><topic>Liver - metabolism</topic><topic>mRNA editing</topic><topic>Protein Biosynthesis - genetics</topic><topic>Protein Transport - genetics</topic><topic>RNA Editing - genetics</topic><topic>RNA, Messenger - genetics</topic><topic>RNA, Messenger - metabolism</topic><topic>Translation</topic><topic>Translocation</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Wang, Ai-Bing</creatorcontrib><creatorcontrib>Liu, De-Pei</creatorcontrib><creatorcontrib>Liang, Chih-Chuan</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Nucleic Acids Abstracts</collection><collection>MEDLINE - Academic</collection><jtitle>Experimental Cell Research</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Wang, Ai-Bing</au><au>Liu, De-Pei</au><au>Liang, Chih-Chuan</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Regulation of human apolipoprotein B gene expression at multiple levels</atitle><jtitle>Experimental Cell Research</jtitle><addtitle>Exp Cell Res</addtitle><date>2003-10-15</date><risdate>2003</risdate><volume>290</volume><issue>1</issue><spage>1</spage><epage>12</epage><pages>1-12</pages><issn>0014-4827</issn><eissn>1090-2422</eissn><abstract>Apolipoprotein B is a large, amphipathic protein that plays a central role in lipoprotein metabolism. Because its overproduction and deficiency leads to metabolic and pathologic disorders, much effort has been paid to investigate the mechanisms of how its homeostasis is achieved. Earlier and recent studies have showed that apoB gene locus might reside in different chromatin domains in the hepatic and intestinal cells, and two sets of very distinct regulatory elements operate to control its transcription. Posttranscriptional modification of apoB mRNA is performed by a multicomponent enzyme complex, several possible pathways regulate the editing efficiency. Understanding of the mechanism responsible for apoB mRNA editing will provide the basis for C-to-U editing in gene therapy. In addition to apoB mRNA abundance and stability, its translation can be also regulated at the steps of elongation. The translocation of apoB into the ER is an important and complicated process that is less understood. 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subjects | Animals Apolipoprotein B Apolipoproteins B - biosynthesis Apolipoproteins B - genetics Apolipoproteins B - metabolism Degradation Gene Expression Regulation - genetics Gene transcription Humans Intestinal Mucosa - metabolism Intestines - cytology Liver - cytology Liver - metabolism mRNA editing Protein Biosynthesis - genetics Protein Transport - genetics RNA Editing - genetics RNA, Messenger - genetics RNA, Messenger - metabolism Translation Translocation |
title | Regulation of human apolipoprotein B gene expression at multiple levels |
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