Identification and characterization of GRIM-1, a cell-death-associated gene product
Using a genome-wide technical knockout, we isolated a newly identified set of GRIM (genes associated with retinoid-interferon-induced mortality) genes; GRIM genes mediate IFN- and retinoic-acid (RA)-induced cell death. Here, we describe the isolation and characterization of one such gene, GRIM-1. Th...
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Veröffentlicht in: | Journal of cell science 2010-08, Vol.123 (16), p.2781-2791 |
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creator | Hofmann, Edward R Nallar, Shreeram C Lin, Limei D'Cunha, Jonathan Lindner, Daniel J Weihua, Xiao Kalvakolanu, Dhananjaya V |
description | Using a genome-wide technical knockout, we isolated a newly identified set of GRIM (genes associated with retinoid-interferon-induced mortality) genes; GRIM genes mediate IFN- and retinoic-acid (RA)-induced cell death. Here, we describe the isolation and characterization of one such gene, GRIM-1. Three proteins, with identical C-termini, were produced from the GRIM-1 open reading frame when this gene was transcribed and translated in vitro. These protein isoforms, designated GRIM-1α, GRIM-1β and GRIM-1γ, differentially suppressed growth via apoptosis in various cell lines. We also show that a caspase-dependent mechanism generates the proapoptotic GRIM-1 isoforms. Lastly, GRIM-1 isoforms differentially blocked maturation of 18S ribosomal RNA, consistent with their respective growth-suppressive ability. Together, these studies identified a novel protein involved in growth suppression and cell death. |
doi_str_mv | 10.1242/jcs.070250 |
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Here, we describe the isolation and characterization of one such gene, GRIM-1. Three proteins, with identical C-termini, were produced from the GRIM-1 open reading frame when this gene was transcribed and translated in vitro. These protein isoforms, designated GRIM-1α, GRIM-1β and GRIM-1γ, differentially suppressed growth via apoptosis in various cell lines. We also show that a caspase-dependent mechanism generates the proapoptotic GRIM-1 isoforms. Lastly, GRIM-1 isoforms differentially blocked maturation of 18S ribosomal RNA, consistent with their respective growth-suppressive ability. Together, these studies identified a novel protein involved in growth suppression and cell death.</description><identifier>ISSN: 0021-9533</identifier><identifier>ISSN: 1477-9137</identifier><identifier>EISSN: 1477-9137</identifier><identifier>DOI: 10.1242/jcs.070250</identifier><identifier>PMID: 20663920</identifier><language>eng</language><publisher>England: The Company of Biologists Limited</publisher><subject>Animals ; Apoptosis - drug effects ; Apoptosis - genetics ; Apoptosis Regulatory Proteins - biosynthesis ; Apoptosis Regulatory Proteins - genetics ; Caspase 9 - metabolism ; Cell Death - drug effects ; Cell Death - genetics ; Cell Growth Processes - genetics ; Gene Expression Regulation ; Gene Knockout Techniques ; HeLa Cells ; Humans ; Interferon-beta - pharmacology ; Mice ; Mice, Nude ; Protein Isoforms ; Proteins - genetics ; RNA, Ribosomal - genetics ; RNA, Ribosomal - metabolism ; Tretinoin - pharmacology</subject><ispartof>Journal of cell science, 2010-08, Vol.123 (16), p.2781-2791</ispartof><rights>2010. 2010</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>230,314,776,780,881,27901,27902</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/20663920$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Hofmann, Edward R</creatorcontrib><creatorcontrib>Nallar, Shreeram C</creatorcontrib><creatorcontrib>Lin, Limei</creatorcontrib><creatorcontrib>D'Cunha, Jonathan</creatorcontrib><creatorcontrib>Lindner, Daniel J</creatorcontrib><creatorcontrib>Weihua, Xiao</creatorcontrib><creatorcontrib>Kalvakolanu, Dhananjaya V</creatorcontrib><title>Identification and characterization of GRIM-1, a cell-death-associated gene product</title><title>Journal of cell science</title><addtitle>J Cell Sci</addtitle><description>Using a genome-wide technical knockout, we isolated a newly identified set of GRIM (genes associated with retinoid-interferon-induced mortality) genes; GRIM genes mediate IFN- and retinoic-acid (RA)-induced cell death. Here, we describe the isolation and characterization of one such gene, GRIM-1. Three proteins, with identical C-termini, were produced from the GRIM-1 open reading frame when this gene was transcribed and translated in vitro. These protein isoforms, designated GRIM-1α, GRIM-1β and GRIM-1γ, differentially suppressed growth via apoptosis in various cell lines. We also show that a caspase-dependent mechanism generates the proapoptotic GRIM-1 isoforms. Lastly, GRIM-1 isoforms differentially blocked maturation of 18S ribosomal RNA, consistent with their respective growth-suppressive ability. Together, these studies identified a novel protein involved in growth suppression and cell death.</description><subject>Animals</subject><subject>Apoptosis - drug effects</subject><subject>Apoptosis - genetics</subject><subject>Apoptosis Regulatory Proteins - biosynthesis</subject><subject>Apoptosis Regulatory Proteins - genetics</subject><subject>Caspase 9 - metabolism</subject><subject>Cell Death - drug effects</subject><subject>Cell Death - genetics</subject><subject>Cell Growth Processes - genetics</subject><subject>Gene Expression Regulation</subject><subject>Gene Knockout Techniques</subject><subject>HeLa Cells</subject><subject>Humans</subject><subject>Interferon-beta - pharmacology</subject><subject>Mice</subject><subject>Mice, Nude</subject><subject>Protein Isoforms</subject><subject>Proteins - genetics</subject><subject>RNA, Ribosomal - genetics</subject><subject>RNA, Ribosomal - metabolism</subject><subject>Tretinoin - pharmacology</subject><issn>0021-9533</issn><issn>1477-9137</issn><issn>1477-9137</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2010</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNpVkEtLA0EQhAdRND4u_gDdmxdXu2d3dnYugoiPgCIYPQ-deSQjyU7c2Qj6611JFD01dH1UUcXYIcIZ8pKfv5p0BhK4gA02wFLKXGEhN9kAgGOuRFHssN2UXgFAciW32Q6HqioUhwEbDa1ruuCDoS7EJqPGZmZKLZnOteFz9Yw-u30aPuR4mlFm3GyWW0fdNKeUognUOZtNXOOyRRvt0nT7bMvTLLmD9d1jLzfXz1d3-f3j7fDq8j73vFZdbgFrIGlcVaNx3HjECsel6EVOkoNHjqgc-fFYVQJJWSpKJFsaYTwIX-yxi5XvYjmeO2v6Ii3N9KINc2o_dKSg_ytNmOpJfNdcoahr6A1O1gZtfFu61Ol5SN_9qHFxmbQsayX60bAnj_5G_Wb8DNkDxyvAU9Q0aUPSLyMOWPQlpShRFV8wQ350</recordid><startdate>20100815</startdate><enddate>20100815</enddate><creator>Hofmann, Edward R</creator><creator>Nallar, Shreeram C</creator><creator>Lin, Limei</creator><creator>D'Cunha, Jonathan</creator><creator>Lindner, Daniel J</creator><creator>Weihua, Xiao</creator><creator>Kalvakolanu, Dhananjaya V</creator><general>The Company of Biologists Limited</general><general>Company of Biologists</general><scope>FBQ</scope><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>7X8</scope><scope>5PM</scope></search><sort><creationdate>20100815</creationdate><title>Identification and characterization of GRIM-1, a cell-death-associated gene product</title><author>Hofmann, Edward R ; Nallar, Shreeram C ; Lin, Limei ; D'Cunha, Jonathan ; Lindner, Daniel J ; Weihua, Xiao ; Kalvakolanu, Dhananjaya V</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-f289t-d0180a7ce681ce2cf1161b452892a720f12119eafbb9651a9da341ad4c5cf05f3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2010</creationdate><topic>Animals</topic><topic>Apoptosis - drug effects</topic><topic>Apoptosis - genetics</topic><topic>Apoptosis Regulatory Proteins - biosynthesis</topic><topic>Apoptosis Regulatory Proteins - genetics</topic><topic>Caspase 9 - metabolism</topic><topic>Cell Death - drug effects</topic><topic>Cell Death - genetics</topic><topic>Cell Growth Processes - genetics</topic><topic>Gene Expression Regulation</topic><topic>Gene Knockout Techniques</topic><topic>HeLa Cells</topic><topic>Humans</topic><topic>Interferon-beta - pharmacology</topic><topic>Mice</topic><topic>Mice, Nude</topic><topic>Protein Isoforms</topic><topic>Proteins - genetics</topic><topic>RNA, Ribosomal - genetics</topic><topic>RNA, Ribosomal - metabolism</topic><topic>Tretinoin - pharmacology</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Hofmann, Edward R</creatorcontrib><creatorcontrib>Nallar, Shreeram C</creatorcontrib><creatorcontrib>Lin, Limei</creatorcontrib><creatorcontrib>D'Cunha, Jonathan</creatorcontrib><creatorcontrib>Lindner, Daniel J</creatorcontrib><creatorcontrib>Weihua, Xiao</creatorcontrib><creatorcontrib>Kalvakolanu, Dhananjaya V</creatorcontrib><collection>AGRIS</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>MEDLINE - Academic</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>Journal of cell science</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Hofmann, Edward R</au><au>Nallar, Shreeram C</au><au>Lin, Limei</au><au>D'Cunha, Jonathan</au><au>Lindner, Daniel J</au><au>Weihua, Xiao</au><au>Kalvakolanu, Dhananjaya V</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Identification and characterization of GRIM-1, a cell-death-associated gene product</atitle><jtitle>Journal of cell science</jtitle><addtitle>J Cell Sci</addtitle><date>2010-08-15</date><risdate>2010</risdate><volume>123</volume><issue>16</issue><spage>2781</spage><epage>2791</epage><pages>2781-2791</pages><issn>0021-9533</issn><issn>1477-9137</issn><eissn>1477-9137</eissn><abstract>Using a genome-wide technical knockout, we isolated a newly identified set of GRIM (genes associated with retinoid-interferon-induced mortality) genes; GRIM genes mediate IFN- and retinoic-acid (RA)-induced cell death. Here, we describe the isolation and characterization of one such gene, GRIM-1. Three proteins, with identical C-termini, were produced from the GRIM-1 open reading frame when this gene was transcribed and translated in vitro. These protein isoforms, designated GRIM-1α, GRIM-1β and GRIM-1γ, differentially suppressed growth via apoptosis in various cell lines. We also show that a caspase-dependent mechanism generates the proapoptotic GRIM-1 isoforms. Lastly, GRIM-1 isoforms differentially blocked maturation of 18S ribosomal RNA, consistent with their respective growth-suppressive ability. Together, these studies identified a novel protein involved in growth suppression and cell death.</abstract><cop>England</cop><pub>The Company of Biologists Limited</pub><pmid>20663920</pmid><doi>10.1242/jcs.070250</doi><tpages>11</tpages><oa>free_for_read</oa></addata></record> |
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subjects | Animals Apoptosis - drug effects Apoptosis - genetics Apoptosis Regulatory Proteins - biosynthesis Apoptosis Regulatory Proteins - genetics Caspase 9 - metabolism Cell Death - drug effects Cell Death - genetics Cell Growth Processes - genetics Gene Expression Regulation Gene Knockout Techniques HeLa Cells Humans Interferon-beta - pharmacology Mice Mice, Nude Protein Isoforms Proteins - genetics RNA, Ribosomal - genetics RNA, Ribosomal - metabolism Tretinoin - pharmacology |
title | Identification and characterization of GRIM-1, a cell-death-associated gene product |
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