The transcription factor STAT2 enhances proteasomal degradation of RCAN1 through the ubiquitin E3 ligase FBW7

► RCAN1 physically interacts with STAT2 in mammalian cells, resulting in decreased RCAN1 protein levels. ► STAT2 reduces RCAN1 levels through the ubiquitin E3 ligase FBW7. ► IFN-α-activated STAT2 enhances the RCAN1 degradation. ► This study provides an evidence of a cytokine-induced RCAN1 degradation pathway involving STAT2 and FBW7.