Abstract
We have recently isolated novel IFN-inducible gene, Gene associated with Retinoid-Interferon-induced Mortality-1 (GRIM-1), using a genetic technique. Moderate ectopic expression of GRIM-1 caused growth inhibition and sensitized cells to retinoic acid (RA)/IFN-induced cell death while high expression caused apoptosis. GRIM-1 depletion, using RNAi, conferred a growth advantage. Three protein isoforms (1α, 1β and 1γ) with identical C-termini are produced from GRIM-1 mRNA. We show that GRIM-1 isoforms interact with NAF1 and DKC1, two essential proteins required for box H/ACA sno/sca RNP biogenesis and suppresses box H/ACA RNA levels in mammalian cells by delocalizing NAF1. Suppression of these small RNAs manifests as inefficient rRNA maturation and growth suppression. Interestingly, yeast Shq1p also caused growth suppression in mammalian cells. Consistent with its growth-suppressive property, GRIM-1 expression is lost in a number of human primary prostate tumors. Our observations support a recent study that GRIM-1 might act as a co-tumor suppressor in the prostate.
Free PMC Article
GRIM-1, a novel growth suppressor, inhibits rRNA maturation by suppressing small nucleolar RNAs
Riferimento:
PLoS One. 2011;6(9):e24082.
Autori:
Nallar SC, Lin L, Srivastava V, Gade P, Hofmann ER, Ahmed H, Reddy SP, Kalvakolanu DV.
Fonte:
PLoS One. 2011;6(9):e24082.
Anno:
2011
Azione:
Una moderato espressione ectopica del gene associato al retinoide-interferone (GRIM-1) causa l'inibizione della crescita e sensibilizza le cellule della prostata all'acido retinoico (RA), mentre una intensa espressione causa apoptosi.
Target:
RA-GRIM1/apoptosi cellule prostatiche.
Sostanze: