Fig. 9.

SCCA1 protects cells against lysosomal injury but enhances apoptosis in response to ER stress. On one hand, SCCA1 blocks necrosis induced by lysosomal injury in response to DNA alkylating damage and hypotonic shock. On the other hand, SCCA1 inhibits lysosomal protein degradation. Hence, in response to ER stress that leads to the accumulation of unfolded proteins, SCCA1 prevents lysosomal clearance of caspase-8/p62 aggregates, resulting in the subsequent activation of caspase-8 and apoptosis.