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The model for zinc-induced apoptosis in cancer cells. Zinc increases the expression of Smad2 and PIAS1, and then promotes the formation of the Smad4/Smad2/PIAS1 complex and its subsequent nuclear translocation. In the nucleus, zinc recruits Smad4/Smad2/PIAS1 complex binding onto SBE1 and SBE3 regions of the p21WAF1/Cip1 promoter, to upregulate the transcription and expression of p21, which facilitates the cell apoptosis as a proapoptotic protein
