Overview of the potential impact of caspase-3 degradation of Inh3 on
cell functions. This diagram shows the potential impact of
caspase-3 on Inh3 degradation within a simplified scheme of the apoptotic
pathways. Since caspase-3 is a primary executioner caspase, Inh3 degradation
is expected to accompany caspase-3-activated apoptotic signaling pathways
whether these are generated through the intrinsic or extrinsic pathways. Inh3
is a potent PP1 inhibitor and controls a significant fraction of the cellular
pool of PP1γ1 and PP1α. In addition, it also controls the
subcellular localization of PP1γ1 to the nucleolus. Degradation of Inh3
leads to release of active PP1 catalytic subunits, which are no longer
restrained to their normal subcellular compartments. As a consequence,
unregulated dephosphorylation of PP1 substrates by the active PP1 catalytic
subunits takes place, leading to disruption of cellular processes. The
circled plus sign is used here to indicate a proapoptotic effect.
Among the PP1 substrates are a subset of those that are involved in apoptotic
signaling pathways. Their unregulated dephosphorylation might also affect
apoptotic signaling. On the right side of the diagram is a
simplified outline of the intrinsic pathway to indicate the interactions of
the Bcl-2 and BH3 family of proteins, of which several, including Bcl-2 and
BAD, have been reported to be regulated by protein phosphatase-1 activity.
Unregulated dephosphorylation of these proteins could produce a proapoptotic
signaling effect. This would provide a potential feedback mechanism that is
shown by the dotted arrow.