Model for the RASSF1A/MOAP-1 proapoptotic pathway. Death receptor-induced cell death (TNFα is used as an example) can result in the recruitment of protein complexes to activate Bax and promote apoptosis. Basally, RASSF1A is kept complexed with 14-3-3 by GSK-3β phosphorylation in order to prevent unwanted recruitment of RASSF1A to death receptor and uncontrolled stimulation of Bax and apoptosis. Once a death receptor stimuli have been received (TNFα as shown above), the TNF-R1/MOAP-1/RASSF1A complex promotes the “open” form of MOAP-1 to associate with Bax. This in turn results in Bax conformational change and recruitment to the mitochondria to initiate cell death. Following release from TNF-R1/MOAP-1 complex, RASSF1A may reassociate with 14-3-3 to prevent continued stimulation of this cell death pathway (unpublished observations). Please see text for further details.
