From procaspase-8 to caspase-8: revisiting structural functions of caspase-8

J Cell Physiol. 2010 Nov;225(2):316-20. doi: 10.1002/jcp.22276.


Caspase-8 is well-characterized to initiate an apoptotic pathway triggered by the external stimuli. The proximity-driven model recently has been proposed to interpret the activation mechanism of caspase-8 in so-far unprecedent detail, in which dimerization, autocleavage, and inhibitor of caspase-8 are indispensable. Intriguingly, death effector domains (DEDs) and ubiquitination after active caspase-8 is released into cytosol can also promote cell apoptosis indirectly. In addition to the proapoptotic role of caspase-8, there is emerging evidence to indicate that the precursor of caspase-8, procaspase-8, has an important function in cell adhesion and migration. Phosphorylation of caspase-8 by c-src controls these functions by preventing the conversion of procaspase-8 to caspase-8. This provides a mechanism to switch these opposing functions. In the migratory role, procaspase-8 interacts with the phosphatidylinositol-3-OH kinase (PI3K) regulatory subunit p85alpha and c-src to modulate signaling by Rac and extracellular signal-regulated kinase (ERK) 1/2, and promotes calpain2 activation. Here, the focus of this review is to highlight three respective aspects of caspase-8, including precursor functions, activation mechanism and maintenance of activity.

Publication types

  • Review

MeSH terms

  • Animals
  • Caspase 8 / chemistry
  • Caspase 8 / metabolism*
  • Enzyme Activation
  • Gene Expression Regulation, Enzymologic
  • Ubiquitination


  • Caspase 8