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. 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-1alpha, GRIM-1beta and GRIM-1gamma, 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.
Hofmann
Edward R
ER
Greenebaum Cancer Center, Department of Microbiology and Immunology, Molecular and Cellular Cancer Biology Track, GPILS, University of Maryland School of Medicine, Baltimore, MD 21201, USA.
Nallar
Shreeram C
SC
Lin
Limei
L
Lindner
Daniel J
DJ
Weihua
Xiao
X
Kalvakolanu
Dhananjaya V
DV
D000818:Animals; D017209:Apoptosis / Q000187:drug effects / Q000235:genetics; D051017:Apoptosis Regulatory Proteins / Q000096:biosynthesis / Q000235:genetics*; D053453:Caspase 9 / Q000378:metabolism; D016923:Cell Death / Q000187:drug effects* / Q000235:genetics*; D048708:Cell Growth Processes / Q000235:genetics; D005786:Gene Expression Regulation; D055786:Gene Knockout Techniques; D006367:HeLa Cells; D006801:Humans; D016899:Interferon-beta / Q000494:pharmacology*; D051379:Mice; D008819:Mice, Nude; D020033:Protein Isoforms; D011506:Proteins / Q000235:genetics; D012335:RNA, Ribosomal / Q000235:genetics / Q000378:metabolism; D014212:Tretinoin / Q000494:pharmacology*
D051017:Apoptosis Regulatory Proteins; D020033:Protein Isoforms; D011506:Proteins; D012335:RNA, Ribosomal; D014212:Tretinoin; D016899:Interferon-beta; D053453:Caspase 9