Unlike Diablo/smac, Grim promotes global ubiquitination and specific degradation of X chromosome-linked inhibitor of apoptosis (XIAP) and neither cause apoptosis.

摘要: Grim is a Drosophila inhibitor of apoptosis (IAP) antagonist that directly interferes with inhibition caspases by IAPs. Expression Grim, or removal DIAP1, sufficient to activate in fly cells. Transient expression mammalian cells induces apoptosis, arguing for the conservation apoptotic pathways, but cytoplasmic IAP Diablo/smac does not. To understand why, we compared and Diablo. Although they have same binding specificity, only promoted XIAP ubiquitination degradation. also synergized promote an increase total cellular ubiquitination, whereas Diablo antagonized this activity. Surprisingly, Grim-induced did not require RING finger. Analysis mutant degradation, was cytotoxic, suggests killing transient assays due combination depletion, blocking IAP-mediated caspase inhibition, at least one other unidentified function. Unlike transiently transfected cells, inducible cell lines can sustain continuous selective degradation without undergoing demonstrating down-regulation antagonism IAPs cause