The human anti-apoptotic proteins cIAP1
and cIAP2 bind but do not inhibit caspases.
Similar to Smac/DIABLO, HtrA2/Omi binds to and neutralizes IAPs (XIAP, cIAP1, and cIAP2) via its N-terminal IAP-binding motif, therefore releasing the inhibition of IAP to caspase-3, -7, and -9.
Our results of weak expression of AIF and HtrA2/Omi in SLL/CLL, combined with previous studies of total lack of Smac/DIABLO expression (9) and variable expression of cIAP1 and cIAP2 in SLL/CLL, (21) appear to support the notion that this lymphoma is characterized by defective apoptosis.
Holcik, "NF45 functions as an IRES trans-acting factor that is required for translation of cIAP1
during the unfolded protein response," Cell Death and Differentiation, vol.
Antagonists induce a conformational change in cIAP1
that promotes autoubiquitination.
AT-406 is a multi-IAP inhibitor (including XIAP, cIAP1
, cIAP2, ML-IAP).
A complex of TRAF2 with cIAP1
, cIAP2, and TRAF1 has further been implicated in the inhibition of TNFR1-induced activation of caspase-8 .
Cellular inhibitor of apoptosis protein 1 and 2 (cIAP1
and cIAP2) are E3 ubiquitin ligases important for ubiquitination of RIP-2 and for signaling downstream of both NOD1 and NOD2.
The TNFR1 complex I comprises the adaptor protein TNFR1-associated death domain protein (TRADD), the death domain-containing protein kinase receptor-interacting protein 1 (RIPK1), and several ubiquitin E3 ligases, including TNFR-associated factor 2 (TRAF2) and cellular inhibitor of apoptosis protein 1 (cIAP1
Authors identified XIAP and cIAP1
as molecular targets of ceramide.