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
Hauptverfasser: Hofmann, Edward R, Nallar, Shreeram C, Lin, Limei, D'Cunha, Jonathan, Lindner, Daniel J, Weihua, Xiao, Kalvakolanu, Dhananjaya V
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container_end_page 2791
container_issue 16
container_start_page 2781
container_title Journal of cell science
container_volume 123
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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source MEDLINE; EZB-FREE-00999 freely available EZB journals; Alma/SFX Local Collection; Company of Biologists
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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