GGCT in Cellular Stress Alleviation
(A, B) Cellular ROS level was quantified by carboxy-H2DCFDA flow cytometry in primary wild-type and GGCT−/− MEFs; error bars represent mean ± SD of four experiments.
(C) GSH level was quantified by mass spectrometry in primary wild-type and GGCT−/− MEFs; error bars represent mean ± SD of three experiments.
(D) L-cysteine level was quantified by mass spectrometry in primary wild-type and GGCT−/− MEFs; error bars represent mean ± SD of three experiments.
(E) The proliferation defect of GGCT−/− MEFs can be rescued by ROS scavenger N-acetylcysteine (NAC, 1 mM) treatment. Error bars represent mean ± SD of three experiments.
(F) Proposed model for GGCT function in cancer. Both oncogenic signal (like RAS activation) and chromosomal 7p14.3 locus amplification lead to GGCT expression up-regulation in human cancers. GGCT helps to alleviate oncogenic stress by regulating GSH-ROS metabolism. In the absence of GGCT, the accumulated cellular stress leads to cell proliferation arrest and cell senescence. For all comparisons, p values of unpaired two-tailed t test are shown.