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Proposed mechanism of CD28 signaling in myeloma cells. Schematic of CD28-mediated pro-survival signaling pathway in MM cells. Under stress conditions, CD28 activates PI3K and Akt, which induces the phosphorylation and inactivation of FoxO3a. Phospho-FoxO3a is excluded from the nucleus and cannot enact its transcriptional program, including transcription of the pro-apoptotic molecule Bim. Dashed arrows indicate inactive pathways.
