cIAP Pan-specific Antibody [B1J9]

Application: Reactivity: Human, Mouse

Usage Information

Dilution
WB1:2000

Application
WB

Reactivity
Human, Mouse

Source
Mouse Monoclonal Antibody

Storage Buffer
PBS, pH 7.2+50% Glycerol+0.05% BSA+0.01% NaN3

Storage (from the date of receipt)
-20°C (avoid freeze-thaw cycles), 2 years

Predicted MW Observed MW
68 kDa 80 kDa
^*Why do the predicted and actual molecular weights differ? The following reasons may explain differences between the predicted and actual protein molecular weight. Post-translational modifications(e.g., phosphorylation, glycosylation); Splice variants and isoforms; Relative charge; Multimerization.

Datasheet & SDS

Biological Description

Specificity
cIAP Pan-specific Antibody [B1J9] detects endogenous levels of total cIAP Pan-specific protein.

Clone
B1J9

Synonym(s)
Cellular inhibitor of apoptosis 2 (C-IAP2), IAP homolog C, hIAP-1; hIAP1, RING finger protein 49, BIRC3, API2, MIHC, RNF49

Background
cIAP1 and cIAP2 are closely related inhibitor of apoptosis family members with N‑terminal tandem baculoviral IAP repeat domains, a central caspase‑recruitment domain, and a C‑terminal RING finger that confers ubiquitin E3 ligase activity, positioning them as scaffold enzymes at TNF receptor–associated signaling complexes and other receptor platforms. The BIR domains bind caspases and other signaling proteins, but sequence analyses and mutagenesis show that cIAP BIRs have substitutions in key residues required for tight caspase inhibition, so their primary biochemical activity arises from RING‑dependent ubiquitination rather than potent direct caspase blockade. The RING domain dimerizes and interacts with ubiquitin‑charged E2 enzymes, catalyzing K63 and other polyubiquitin chains on substrates such as RIP1 at the TNF receptor 1 complex, which creates docking sites for TAK1, IKK, and other NF‑κB pathway components and supports prosurvival and proinflammatory transcriptional responses after TNFα stimulation. Either cIAP1 or cIAP2 is sufficient to maintain RIP1 polyubiquitination and NF‑κB activation upon TNFα treatment, and genetic loss of both proteins leads to reduced RIP1 ubiquitination, diminished NF‑κB signaling, and increased formation of RIP1–FADD–caspase‑8 complexes that execute apoptosis. cIAPs also autoubiquitinate and ubiquitinate other adaptors in TNF and related pathways, contributing to turnover of components and to the balance between survival signaling and cell death complexes in response to cytokine and pattern‑recognition receptor inputs. Mitochondria‑derived Smac/DIABLO and HtrA2/Omi bind the BIR domains through IAP‑binding motifs and promote RING‑dependent autoubiquitination and proteasomal degradation of cIAP1 and cIAP2, which lowers cellular cIAP levels and shifts signaling from NF‑κB activation toward caspase‑8 activation and apoptosis in death receptor pathways. Small‑molecule Smac mimetics bind cIAP BIRs, relieve intramolecular inhibition of the RING domain, induce rapid RING‑mediated autoubiquitination, and trigger proteasomal clearance of cIAP1 and, to a lesser extent, cIAP2, providing a tool to experimentally deplete cIAPs and study the resulting switch from prosurvival to proapoptotic signaling. Elevated cIAP1 and cIAP2 expression is reported in multiple cancers, and their E3 ligase activity toward RIP1 and other targets has been linked to maintenance of constitutive NF‑κB activity and survival of malignant cells under stress, while pharmacologic or genetic disruption of cIAP function sensitizes tumor cells to TNF family ligands and chemotherapeutic agents.

Background

cIAP1 and cIAP2 are closely related inhibitor of apoptosis family members with N‑terminal tandem baculoviral IAP repeat domains, a central caspase‑recruitment domain, and a C‑terminal RING finger that confers ubiquitin E3 ligase activity, positioning them as scaffold enzymes at TNF receptor–associated signaling complexes and other receptor platforms. The BIR domains bind caspases and other signaling proteins, but sequence analyses and mutagenesis show that cIAP BIRs have substitutions in key residues required for tight caspase inhibition, so their primary biochemical activity arises from RING‑dependent ubiquitination rather than potent direct caspase blockade. The RING domain dimerizes and interacts with ubiquitin‑charged E2 enzymes, catalyzing K63 and other polyubiquitin chains on substrates such as RIP1 at the TNF receptor 1 complex, which creates docking sites for TAK1, IKK, and other NF‑κB pathway components and supports prosurvival and proinflammatory transcriptional responses after TNFα stimulation. Either cIAP1 or cIAP2 is sufficient to maintain RIP1 polyubiquitination and NF‑κB activation upon TNFα treatment, and genetic loss of both proteins leads to reduced RIP1 ubiquitination, diminished NF‑κB signaling, and increased formation of RIP1–FADD–caspase‑8 complexes that execute apoptosis. cIAPs also autoubiquitinate and ubiquitinate other adaptors in TNF and related pathways, contributing to turnover of components and to the balance between survival signaling and cell death complexes in response to cytokine and pattern‑recognition receptor inputs. Mitochondria‑derived Smac/DIABLO and HtrA2/Omi bind the BIR domains through IAP‑binding motifs and promote RING‑dependent autoubiquitination and proteasomal degradation of cIAP1 and cIAP2, which lowers cellular cIAP levels and shifts signaling from NF‑κB activation toward caspase‑8 activation and apoptosis in death receptor pathways. Small‑molecule Smac mimetics bind cIAP BIRs, relieve intramolecular inhibition of the RING domain, induce rapid RING‑mediated autoubiquitination, and trigger proteasomal clearance of cIAP1 and, to a lesser extent, cIAP2, providing a tool to experimentally deplete cIAPs and study the resulting switch from prosurvival to proapoptotic signaling. Elevated cIAP1 and cIAP2 expression is reported in multiple cancers, and their E3 ligase activity toward RIP1 and other targets has been linked to maintenance of constitutive NF‑κB activity and survival of malignant cells under stress, while pharmacologic or genetic disruption of cIAP function sensitizes tumor cells to TNF family ligands and chemotherapeutic agents.

References
https://pubmed.ncbi.nlm.nih.gov/18570872/ https://pubmed.ncbi.nlm.nih.gov/18697935/

Protein Size (kDa)	PVDF Transfer Membrane Pore Size (μm)
< 10	0.22
10-20	0.22
20-30	0.45
30-45	0.45
45-70	0.45
80-100	0.45
100-140	0.45
> 140	0.45

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Protein Size (kDa)	Separating Gel Percentage
4-40	20%
12-45	15%
10-70	12.5%
15-100	10%
25-100	8%
60-210	5%