Transcriptional control of cystine/glutamate transporter gene by amino acid deprivation

The growth inhibitory effect of actein on human breast cancer cells is associated with activation of stress response pathways

“…All of these 5 stress response genes are induced by activating transcription factor 4 (ATF4), which mediates the ISR pathway. 14,15,33,34,35 Indeed, there was significant upregulation (p < 0.05) of ATF4 after 3 of the 4 treatment conditions (Table I, panel D). In addition, actein significantly altered (p < 0.05) the expression of three other components of the ISR (Table I, panel D), under at least one of the treatment conditions, including: GRP78, a calcium-dependent ER stress molecular chaperone, PERK (p-value <0.10) and GADD34.…”

System xc−Activity and Astrocytes Are Necessary for Interleukin-1β-Mediated Hypoxic Neuronal Injury

“…Indeed, after IL-1␤ treatment, a significant increase in the velocity (V max ) of System x c Ϫ was found. Whether this increased activity is associated with an upregulation of transporter expression (Sato et al, 1999(Sato et al, , 2004Gochenauer and Robinson, 2001;Sheldon et al, 2006;Goltz et al, 2007) or perhaps is a result of a posttranslational modification that alters transporter kinetics (Baker et al, 2002;Xi et al, 2003) remains to be determined. Although selective inhibitors for System x c Ϫ are not available at this time, several carboxyphenylglycine derivatives (i.e., 4-CPG and LY367385), mostly marketed as mGluR1 antagonists, were used to inhibit this transporter (Gochenauer and Robinson, 2001) and were found to be effective against the IL-1␤-mediated potentiation of hypoxic neuronal cell death.…”

Cystathionine Is a Novel Substrate of Cystine/Glutamate Transporter

“…3 It seems an appealing hypothesis that cystathionine transported via system x c Ϫ plays an important role in preventing steatosis in the thymus. We have previously demonstrated that xCT is induced by endoplasmic reticulum stress caused by amino acid deprivation or the endoplasmic reticulum stress-inducing agent tunicamycin and that the induction is mediated by a genomic cis-element termed the amino acid response element and a transcription factor, activating transcription factor 4 (ATF4) (40). Recently, Dickhout et al (41) have demonstrated that Cgl is up-regulated by the ATF4 pathway under endoplasmic reticulum stress conditions.…”