Prelamin A Farnesylation and Progeroid Syndromes
Hutchinson-Gilford progeria syndrome (HGPS) is caused by a LMNA mutation that leads to the synthesis of a mutant prelamin A that is farnesylated but cannot be further processed to mature lamin A. A more severe progeroid disorder, restrictive dermopathy (RD), is caused by the loss of the prelamin A-p...
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| Veröffentlicht in: | The Journal of biological chemistry 2006-12, Vol.281 (52), p.39741-39745 |
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| container_issue | 52 |
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| container_title | The Journal of biological chemistry |
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| creator | Young, Stephen G. Meta, Margarita Yang, Shao H. Fong, Loren G. |
| description | Hutchinson-Gilford progeria syndrome (HGPS) is caused by a LMNA mutation that leads to the synthesis of a mutant prelamin A that is farnesylated but cannot be further processed to mature lamin A. A more severe progeroid disorder, restrictive dermopathy (RD), is caused by the loss of the prelamin A-processing enzyme, ZMPSTE24. The absence of ZMPSTE24 prevents the endoproteolytic processing of farnesyl-prelamin A to mature lamin A and leads to the accumulation of farnesyl-prelamin A. In both HGPS and RD, the farnesyl-prelamin A is targeted to the nuclear envelope, where it interferes with the integrity of the nuclear envelope and causes misshapen cell nuclei. Recent studies have shown that the frequency of misshapen nuclei can be reduced by treating cells with a farnesyltransferase inhibitor (FTI). Also, administering an FTI to mouse models of HGPS and RD ameliorates the phenotypes of progeria. These studies have prompted interest in testing the efficacy of FTIs in children with HGPS. |
| doi_str_mv | 10.1074/jbc.R600033200 |
| format | Article |
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A more severe progeroid disorder, restrictive dermopathy (RD), is caused by the loss of the prelamin A-processing enzyme, ZMPSTE24. The absence of ZMPSTE24 prevents the endoproteolytic processing of farnesyl-prelamin A to mature lamin A and leads to the accumulation of farnesyl-prelamin A. In both HGPS and RD, the farnesyl-prelamin A is targeted to the nuclear envelope, where it interferes with the integrity of the nuclear envelope and causes misshapen cell nuclei. Recent studies have shown that the frequency of misshapen nuclei can be reduced by treating cells with a farnesyltransferase inhibitor (FTI). Also, administering an FTI to mouse models of HGPS and RD ameliorates the phenotypes of progeria. These studies have prompted interest in testing the efficacy of FTIs in children with HGPS.</description><identifier>ISSN: 0021-9258</identifier><identifier>EISSN: 1083-351X</identifier><identifier>DOI: 10.1074/jbc.R600033200</identifier><identifier>PMID: 17090536</identifier><language>eng</language><publisher>United States: Elsevier Inc</publisher><subject>Animals ; Humans ; Lamin Type A ; Nuclear Proteins - chemistry ; Nuclear Proteins - genetics ; Nuclear Proteins - metabolism ; Nuclear Proteins - physiology ; Progeria - etiology ; Progeria - genetics ; Progeria - metabolism ; Progeria - pathology ; Protein Precursors - chemistry ; Protein Precursors - genetics ; Protein Precursors - metabolism ; Protein Precursors - physiology ; Protein Prenylation - genetics ; Syndrome</subject><ispartof>The Journal of biological chemistry, 2006-12, Vol.281 (52), p.39741-39745</ispartof><rights>2006 © 2006 ASBMB. 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A more severe progeroid disorder, restrictive dermopathy (RD), is caused by the loss of the prelamin A-processing enzyme, ZMPSTE24. The absence of ZMPSTE24 prevents the endoproteolytic processing of farnesyl-prelamin A to mature lamin A and leads to the accumulation of farnesyl-prelamin A. In both HGPS and RD, the farnesyl-prelamin A is targeted to the nuclear envelope, where it interferes with the integrity of the nuclear envelope and causes misshapen cell nuclei. Recent studies have shown that the frequency of misshapen nuclei can be reduced by treating cells with a farnesyltransferase inhibitor (FTI). Also, administering an FTI to mouse models of HGPS and RD ameliorates the phenotypes of progeria. These studies have prompted interest in testing the efficacy of FTIs in children with HGPS.</description><subject>Animals</subject><subject>Humans</subject><subject>Lamin Type A</subject><subject>Nuclear Proteins - chemistry</subject><subject>Nuclear Proteins - genetics</subject><subject>Nuclear Proteins - metabolism</subject><subject>Nuclear Proteins - physiology</subject><subject>Progeria - etiology</subject><subject>Progeria - genetics</subject><subject>Progeria - metabolism</subject><subject>Progeria - pathology</subject><subject>Protein Precursors - chemistry</subject><subject>Protein Precursors - genetics</subject><subject>Protein Precursors - metabolism</subject><subject>Protein Precursors - physiology</subject><subject>Protein Prenylation - genetics</subject><subject>Syndrome</subject><issn>0021-9258</issn><issn>1083-351X</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2006</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqF0EtLAzEUBeAgitbq1qXMQtxNvXnMTLIsxRcIig9wFzKTOzYyM6lJq_TfG2nBlbi6m-8eDoeQEwoTCpW4eK-byWMJAJwzgB0yoiB5zgv6uktGAIzmihXygBzG-J4UCEX3yQGtQEHByxGBh4Cd6d2QTbMrEwaM684snR8yM9jsIfg3DN7Z7Gk92OB7jEdkrzVdxOPtHZOXq8vn2U1-d399O5ve5Y0QbJkjSFRSitaauoaWUStLaStUyjJbCUMRlJG0rXgBJVe8qKjkogSVClqjgI_J-SZ3EfzHCuNS9y422HVmQL-KupSsLCmofyFVxU-qSHCygU3wMQZs9SK43oS1pqB_xtRpTP07Zno43Sav6h7tL9-ul8DZBszd2_zLBdS1880ce80k1QXTXFWCJiY3DNNenw6Djo3DoUGbXpqltt79VeEb9HmL-g</recordid><startdate>20061229</startdate><enddate>20061229</enddate><creator>Young, Stephen G.</creator><creator>Meta, Margarita</creator><creator>Yang, Shao H.</creator><creator>Fong, Loren G.</creator><general>Elsevier Inc</general><general>American Society for Biochemistry and Molecular Biology</general><scope>6I.</scope><scope>AAFTH</scope><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>8FD</scope><scope>FR3</scope><scope>P64</scope><scope>RC3</scope><scope>7X8</scope></search><sort><creationdate>20061229</creationdate><title>Prelamin A Farnesylation and Progeroid Syndromes</title><author>Young, Stephen G. ; Meta, Margarita ; Yang, Shao H. ; Fong, Loren G.</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c442t-e08e9884fdabb0f21d868d7e99d2d74a1e09a81f73506393571834609491da903</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2006</creationdate><topic>Animals</topic><topic>Humans</topic><topic>Lamin Type A</topic><topic>Nuclear Proteins - chemistry</topic><topic>Nuclear Proteins - genetics</topic><topic>Nuclear Proteins - metabolism</topic><topic>Nuclear Proteins - physiology</topic><topic>Progeria - etiology</topic><topic>Progeria - genetics</topic><topic>Progeria - metabolism</topic><topic>Progeria - pathology</topic><topic>Protein Precursors - chemistry</topic><topic>Protein Precursors - genetics</topic><topic>Protein Precursors - metabolism</topic><topic>Protein Precursors - physiology</topic><topic>Protein Prenylation - genetics</topic><topic>Syndrome</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Young, Stephen G.</creatorcontrib><creatorcontrib>Meta, Margarita</creatorcontrib><creatorcontrib>Yang, Shao H.</creatorcontrib><creatorcontrib>Fong, Loren G.</creatorcontrib><collection>ScienceDirect Open Access Titles</collection><collection>Elsevier:ScienceDirect:Open Access</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</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>The Journal of biological chemistry</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Young, Stephen G.</au><au>Meta, Margarita</au><au>Yang, Shao H.</au><au>Fong, Loren G.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Prelamin A Farnesylation and Progeroid Syndromes</atitle><jtitle>The Journal of biological chemistry</jtitle><addtitle>J Biol Chem</addtitle><date>2006-12-29</date><risdate>2006</risdate><volume>281</volume><issue>52</issue><spage>39741</spage><epage>39745</epage><pages>39741-39745</pages><issn>0021-9258</issn><eissn>1083-351X</eissn><abstract>Hutchinson-Gilford progeria syndrome (HGPS) is caused by a LMNA mutation that leads to the synthesis of a mutant prelamin A that is farnesylated but cannot be further processed to mature lamin A. A more severe progeroid disorder, restrictive dermopathy (RD), is caused by the loss of the prelamin A-processing enzyme, ZMPSTE24. The absence of ZMPSTE24 prevents the endoproteolytic processing of farnesyl-prelamin A to mature lamin A and leads to the accumulation of farnesyl-prelamin A. In both HGPS and RD, the farnesyl-prelamin A is targeted to the nuclear envelope, where it interferes with the integrity of the nuclear envelope and causes misshapen cell nuclei. Recent studies have shown that the frequency of misshapen nuclei can be reduced by treating cells with a farnesyltransferase inhibitor (FTI). Also, administering an FTI to mouse models of HGPS and RD ameliorates the phenotypes of progeria. These studies have prompted interest in testing the efficacy of FTIs in children with HGPS.</abstract><cop>United States</cop><pub>Elsevier Inc</pub><pmid>17090536</pmid><doi>10.1074/jbc.R600033200</doi><tpages>5</tpages><oa>free_for_read</oa></addata></record> |
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| source | MEDLINE; Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals; PubMed Central; Alma/SFX Local Collection |
| subjects | Animals Humans Lamin Type A Nuclear Proteins - chemistry Nuclear Proteins - genetics Nuclear Proteins - metabolism Nuclear Proteins - physiology Progeria - etiology Progeria - genetics Progeria - metabolism Progeria - pathology Protein Precursors - chemistry Protein Precursors - genetics Protein Precursors - metabolism Protein Precursors - physiology Protein Prenylation - genetics Syndrome |
| title | Prelamin A Farnesylation and Progeroid Syndromes |
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