(i) HuR knockdown (via LMB and siRNAs) [down arrow] cytoplasmic HuR and cIAP2
(concentration dependent) Kakuguchi et al.
They found that cIAP2, which functions by modifying and activating survival factors in the cell, steers the body away from an inflammatory and auto-destructive process known as necrotic death.
In its absence, the same factors that depend on cIAP2 to keep the cell alive, reveal a destructive side and induce a harmful form of cell death.
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.
Intracellular S1P synthesized by SphK1 was required to activate the apoptosis inhibitor cIAP2
for Lys63- (K63-) linked polyubiquitination of newly synthesized IRF1 and chemokine synthesis .
therefore not only protects the infected cells from dying in such a manner, but also protects uninfected neighboring cells in the same tissue.
(302) However, although apoptosis-inducing genes such as TNF-[alpha] and TNF-related apoptosis-inducing ligand are highly expressed, the cells are likely protected from apoptosis due to expression of the caspase-8 antagonist cFLIP (cellular FLICE inhibitory protein), the caspase inhibitor cIAP2
, and the antioxidant enzyme manganese superoxide dismutase.
A few intracellular targets of S1P signaling that are relevant for inflammatory events have been identified, including TNF-a receptor-associated factor 2 (TRAF2), an E3 ubiquitin ligase of the nuclear factor "kappa-light-chain-enhancer" of activated B-cells (NF-kB) pathway , inhibitor of apoptosis 2 (cIAP2
), which promotes polyubiquitination of interferon regulatory factor-1 to enhance chemokine expression , class I histone deacetylases HDAC1 and HDAC2 , and the mitophagy receptor prohibitin 2 .
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.
Lefebvre et al., "Inhibitor of apoptosis protein cIAP2
is essential for lipopolysaccharide-induced macrophage survival," Molecular and Cellular Biology, vol.