Activation of membrane-bound transcription factors of the CREB3 subfamily. CREB3 subfamily proteins are anchored to the ER membrane in an inactive form when they are not stimulated. Only upon stimulation, the CREB3 subfamily proteins are translocated by COPII vesicles from the ER to the Golgi apparatus where they will encounter S1P and S2P proteases. They are cleaved to release the N-terminal fragments which will enter the nucleus to activate transcription of target genes. CREB3 subfamily proteins might work as homodimers or heterodimers in the nucleus to activate gene expression.