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Abstract
Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) serves as an extracellular signal that triggers apoptosis in tumor cells. To characterize the molecular events involved in TRAIL-induced apoptotic signaling, we investigated the role of extracellular signal-regulated kinase 1/2 (ERK1/2) in HeLa cell death. Here we show that TRAIL-activated ERK1/2 through a tyrosine kinase-dependent pathway, subsequently elevated anti-apoptotic Bcl-2 protein levels. ERK1/2 inhibition with PD98059 promoted apoptotic cell death through the downregulation of ERK1/2 activity and Bcl-2 protein levels. Moreover, tyrosine kinase inhibition with Genistein in TRAIL-induced apoptosis effectively attenuated ERK1/2 activity and enhanced apoptotic cell death. Taken together, our results indicate that ERK1/2 activation via tyrosine kinase pathway plays a protective role as the cellular defense mechanism through the upregulation of Bcl-2 protein levels in TRAIL-induced apoptosis.