Fig. 7: Mechanism of apoptotic regulation by the CREB1-RASAL2-BCL2 axis.
From: CREB1-BCL2 drives mitochondrial resilience in RAS GAP-dependent breast cancer chemoresistance
RASAL2 and BCL2 share common transcription factor motifs in their promoter regions. Transcription factor CREB1 binds to these promoter regions, and drives the expression of RASAL2 and BCL2. This upregulation is supported by CREB1-interactor YAP, a transcription co-factor that is regulated by RASAL2, thus forming a positive loop in the CREB1-RASAL2-BCL2 axis. Both RASAL2 and BCL2 colocalise at the mitochondria. Their presence confers mitochondrial resilience by mitigating mitochondrial outer membrane depolarisation, which occurs, for example, during BAX/tBID-triggered apoptosis. Consequently, in high RASAL2/BCL2 chemoresistant tumour cells, there is reduced cytochrome c release upon apoptosis induction and thereby attenuation of cell death.
