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Example sentences for: gadd
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The Rat Genome U34 array was found to contain probe-sets representing the ER chaperones glucose-regulated protein (GRP) 78, protein disulfide isomerase, GRP94, calreticulin and endoplasmic reticulum protein 29 (EPR29), GADD153 and PERK.
The genes selected for confirmation were those for cyclin D1, GADD45, GPX, HO-1, HSP70, Mdr-1, QR, prostaglandin H synthase (PGHS), p21WAF1/CIP1 and PLA2.
Two highly conserved responses are observed under conditions of endoplasmic reticulum (ER) stress; the ER overload and unfolded protein responses [ 24 25 ] . The unfolded protein response is characterized by generalized suppression of protein synthesis and the specific induction of ER-resident proteins and GADD153 [ 24 ] . The transcription factor nuclear factor kB is activated during the ER overload response, leading to the downstream induction of pro-inflammatory proteins [ 25 ] . Therefore, the transcriptional modulation of GADD153 and IkB by mefloquine suggests that the ER might be a target of the drug.
The first, the ER overload response, triggers the activation of the transcription factor NFkB and the subsequent upregulation of inflammatory proteins [ 13 ] . The second, the unfolded protein response (UPR) induces three divergent cellular events: (i) the activation of transcription factor ATF6 leading to the upregulation of ER chaperones such as protein disulfide isomerase, (ii) upregulation of the pro-apoptotic transcription factor GADD153 and (iii) suppression of protein synthesis via phosphorylation of eukaryotic translation initiation factor 2α (eIF2α) by pancreatic eIF2α kinase (PEK/PERK, [ 11 12 ] ). Upregulation of the ER chaperones, GADD153 and PERK in response to a toxic insult would constitute direct evidence of an ER stress response.
Indeed, C/EBPα activates transcription of the p21 [ 37 ] , gadd45 [ 5 6 ] , gas2 and gas3 [ 38 39 ] genes.
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