title: From procaspase-8 to caspase-8: revisiting structural functions of caspase-8.
abstract: 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.
authors.affiliation: Department of Oncology, The First Affiliated Hospital of Medical School of Xi'an Jiao Tong University, Xi'an Shaanxi Province, PR China. szhaoy@126.com
authors.forename: Yang
authors.initials: Y
authors.lastname: Zhao
authors.forename: Xin
authors.initials: X
authors.lastname: Sui
authors.forename: Hong
authors.initials: H
authors.lastname: Ren
mesh_terms: D000818:Animals; D053181:Caspase 8 / Q000737:chemistry / Q000378:metabolism*; D004789:Enzyme Activation; D015971:Gene Expression Regulation, Enzymologic; D054875:Ubiquitination
chemical_list: D053181:Caspase 8