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Schematic pathways of SAR-mediated globin gene induction. Enforced SAR expression alone can replicate the known effects of HU on K562 cells, including cytotoxicity (apoptosis), G1/S-phase arrest, and γ-globin induction. SAR-induced GATA-2 expression not only increases γ-globin gene induction, it also induces p21 protein. Induction of p21 causes inhibition of cell proliferation and G1/S arrest. Reduction of PI3 kinase (PI3K) and phosphorylated ERK (pERK) can be triggered by SAR.
