The effects of $\gamma$-GCSh overexpression on cellular Cu metabolism and CDDP transport. Overexpression of $\gamma$-GCSh, which catalyzes the ligation of cysteine (Cys) and glutamate (Glu), results in increased GSH levels. Excess GSH functions as a Cu depletor, as evidenced by the reduction in CCO and SOD activity, and holo-ceruloplasmin (Cu-Cpm) contents. Intracellular Cu deficiency upregulates hCtr1 expression, which is regulated by transcription factor, Sp1. Upregulation of hCtr1 enhances CDDP uptake, resulting in elevated sensitivities to CDDP treatment. CCS, HAH1, and COX17 are Cu chaperones that shuffle Cu to their respective targets as indicated by arrows.