XIAP, also called baculoviral IAP repeat-containing protein 4 (BIRC4), is a potent suppressor of apoptosis that directly inhibits specific members of the caspase family of cysteine proteases, including caspase-3, -7, and -9 [, ]. It promotes proteasomal degradation of caspase-3 and enhances its anti-apoptotic effect in Fas-induced cell death []. The ubiquitin-protein ligase (E3) activity of XIAP also exhibits in the ubiquitination of second mitochondria-derived activator of caspases (Smac) []. The mitochondrial proteins, Smac/DIABLO and Omi/HtrA2, can inhibit the antiapoptotic activity of XIAP []. XIAP has also been implicated in several intracellular signaling cascades involved in the cellular response to stress, such as the c-Jun N-terminal kinase (JNK) pathway, the nuclear factor-kappaB (NF-kappaB) pathway, and the transforming growth factor-beta (TGF-beta) pathway [, , ]. Moreover, XIAP can regulate copper homeostasis through interacting with MURR1 []. BIRC8, also called inhibitor of apoptosis-like protein 2 (IAP-like protein 2 or ILP-2), or testis-specific inhibitor of apoptosis, is a tissue-specific homologue of E3 ubiquitin-protein ligase XIAP. It has been implicated in the control of apoptosis in the testis by direct inhibition of caspase 9 []. Both XIAP and BIRC8 contain three N-terminal baculoviral IAP repeat (BIR) domains, a ubiquitin-association (UBA) domain and a RING domain at the carboxyl terminus.This entry represents the UBA domain found in XIAP and BIRC8.
XAF1 (X-linked inhibitor of apoptosis (XIAP)-associated factor 1) is a proapoptotic protein that antagonises the caspase-inhibitory activity of XIAP [, ]. It is a tumor suppressor that is frequently inactivated in many human cancers. It forms a positive feedback loop with p53 and acts as a molecular switch in p53-mediated cell-fate decisions favoring apoptosis over cell-cycle arrest [].
Caspase-6 (EC 3.4.22.59; MEROPS identifier C14.005) is a cysteine endopeptidase from family C14. It cleaves aspartyl bonds, and has a preference for Val in P4, Glu or Gln in P3, His or Val in P2 and Gly in P1' [, ]similar to the initiator caspases 8 and 9 []. Caspase-6 processes its own precursor to generate a two-chain form [, ]and lamin A []and STAB1 [], which are not cleaved by caspases 3 or 7. Unusually, caspase-6 activity is unaffected by XIAP []. Caspase-6 is an initiator caspase activated by caspases 3 and 7 []and activating caspase-8 [, ]. It also translocates to the nucleus where processing of lamin A occurs.This entry also includes SfAV caspase from Spodoptera frugiperda ascovirus (MEROPS identifier C14.037), which is an executioner caspase that can induce apoptosis in host insect cells [].
