Affinage

BIRC2

Baculoviral IAP repeat-containing protein 2 · UniProt Q13490

Length
618 aa
Mass
69.9 kDa
Annotated
2026-06-09
100 papers in source corpus 57 papers cited in narrative 57 extracted findings
Cross-family judge vs UniProt: Affinage preferred faithfulness: 7/7 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

BIRC2/cIAP1 is a RING-domain E3 ubiquitin ligase that functions as a central post-translational rheostat of TNF-receptor-superfamily signaling, determining whether cells survive or die (PMID:18570872, PMID:31141691). Within the TNF-R1 signaling complex, to which it is recruited through TRADD-mediated association with TRAF2 (PMID:8943045), cIAP1 (redundantly with cIAP2) constitutively conjugates K63-, K11-, and linear ubiquitin chains onto RIP1, generating the platform that recruits TAK1/IKK to drive canonical NF-κB activation while preventing RIP1 from nucleating pro-death complexes with caspase-8 or RIP3-dependent necrosomes (PMID:18570872, PMID:18621737, PMID:21113135, PMID:21052097). This ligase activity, executed with UbcH5-family E2 enzymes, extends across the RIP-kinase family (RIP1–RIP4) and to RIP2 in NOD1/NOD2 innate immune signaling and caspase-1 in inflammasome activation (PMID:19258326, PMID:19464198, PMID:21931591, PMID:22195745). cIAP1 also sets the threshold for non-canonical NF-κB by targeting NIK for proteasomal degradation within a TRAF2–TRAF3 complex, and terminates TNF-R2 signaling by ubiquitinating TRAF2 and ASK1 (PMID:18997794, PMID:11907583, PMID:17220297). In vivo, combined cIAP1/2 loss causes caspase-8-dependent intestinal and hepatic death, establishing suppression of caspase-8 apoptosis as the core survival function (PMID:31141691). Although its BIR domains bind caspases-3 and -7, cIAP1 promotes their proteasomal degradation rather than directly inhibiting their activity (PMID:16339151, PMID:19258326). The enzyme is autoinhibited by a CARD domain that blocks RING dimerization and E2 activation (PMID:21549626), stabilized by the chaperone HSP90β and the deubiquitinases OTUB1 and USP19 (PMID:18239673, PMID:23524849, PMID:33712742, PMID:21849505), and selectively eliminated by Smac/DIABLO or synthetic IAP antagonists that bind its BIR3 domain and trigger RING-dependent auto-ubiquitination and proteasomal degradation (PMID:14960576, PMID:18230607, PMID:20356846). Beyond cytoplasmic signaling, nuclear cIAP1 binds E2F1 and stabilizes it through K63-linked ubiquitination to promote cell-cycle gene transcription (PMID:21653699, PMID:28542143).

Mechanistic history

Synthesis pass · year-by-year structured walk · 15 steps
  1. 1996 High

    Established that cIAP1 is physically positioned within TNF receptor signaling, identifying how it gains access to the death-and-survival machinery via the TRADD-TRAF2 adaptor module.

    Evidence Co-immunoprecipitation and TNF-dependent recruitment assays in cells

    PMID:8943045

    Open questions at the time
    • Did not define a catalytic activity or downstream substrate at the receptor complex
  2. 1997 High

    First assigned cIAP1 an anti-apoptotic biochemical activity by showing BIR-domain binding to caspases-3/-7, initially interpreted as direct enzymatic inhibition.

    Evidence In vitro binding and caspase activity assays with recombinant proteins, cell-free cytochrome-c system

    PMID:9384571

    Open questions at the time
    • The inferred direct inhibition was later overturned for cIAP BIRs
    • Did not address the RING/E3 contribution
  3. 2002 High

    Reframed cIAP1 as an E3 ubiquitin ligase rather than a stoichiometric inhibitor, by demonstrating it ubiquitinates TRAF2 for proteasomal degradation downstream of TNF-R2.

    Evidence In vitro ubiquitination with purified components, E3-defective mutant, proteasome inhibition in primary cells

    PMID:11907583

    Open questions at the time
    • Did not identify the full substrate repertoire
    • E2 partner and chain linkage unresolved at this stage
  4. 2008 High

    Resolved the core survival mechanism: cIAP1/2 maintain constitutive ubiquitination of RIP1 that recruits TAK1 for NF-κB while blocking caspase-8 association, defining a molecular survival/death switch.

    Evidence IAP antagonist treatment, in vitro reconstitution with purified cIAP1+UbcH5a, RIP1-TAK1/RIP1-caspase-8 co-IPs, genetic and siRNA ablation

    PMID:18570872 PMID:18621737 PMID:18697935

    Open questions at the time
    • Did not resolve which ubiquitin linkages dominate in vivo
    • Redundancy with cIAP2 left the unique cIAP1 contribution unclear
  5. 2008 High

    Defined cIAP1 as the threshold-setter for non-canonical NF-κB by showing it degrades NIK within a TRAF2/TRAF3 complex, linking IAP loss to constitutive RelB activation.

    Evidence Complex reconstitution, genetic and pharmacological cIAP inhibition, NIK degradation and primary B cell assays

    PMID:18997794

    Open questions at the time
    • Did not establish chain linkage on NIK
    • Stoichiometry within the TRAF2/TRAF3 complex undefined
  6. 2008 Medium

    Identified the mechanism by which IAP antagonists kill: Smac/DIABLO binds BIR domains to stimulate RING-dependent cIAP1 auto-ubiquitination and selective degradation.

    Evidence In vitro auto-ubiquitination, Smac N-terminal peptide sufficiency, E2 identification, proteasome inhibition

    PMID:14960576 PMID:18230607

    Open questions at the time
    • Did not fully define the conformational activation step
    • Selectivity over XIAP/cIAP2 mechanism incomplete
  7. 2009 High

    Overturned the direct-caspase-inhibitor model by showing cIAP1 binds and ubiquitinates caspases-3/-7 for degradation without inhibiting their catalytic activity.

    Evidence In vitro binding, fluorogenic substrate assays, ubiquitination with UbcH5/UbcH8, chimeric caspase-3, domain mapping

    PMID:16339151 PMID:19258326

    Open questions at the time
    • In vivo contribution of caspase degradation versus RIP1 control not separated
  8. 2009 High

    Extended cIAP1 function into innate immunity by identifying RIP2 ubiquitination as required for NOD1/NOD2 signaling.

    Evidence Birc2/Birc3 knockout macrophages, RIP2 ubiquitination assay, in vivo NOD agonist challenge and colitis model

    PMID:19464198

    Open questions at the time
    • Relative contribution of cIAP1 versus cIAP2 to RIP2 modification not isolated
  9. 2010 High

    Mapped the ubiquitin chain architecture on RIP1, showing cIAP1/UbcH5 assemble K11-linked chains read by NEMO, diversifying the chain code at the receptor complex.

    Evidence Yeast two-hybrid E2 screen, in vitro reconstitution, mass spectrometry of linkages, TNFR1 complex IP

    PMID:21113135

    Open questions at the time
    • Relative in vivo abundance of K11 versus K63 chains not quantified
  10. 2011 High

    Explained how cIAP1 E3 activity is restrained, with a crystal structure showing the CARD domain autoinhibits by preventing RING dimerization and E2 activation.

    Evidence CARD crystal structure, RING dimerization and E2 activation assays, mutagenesis, zebrafish vascular readout

    PMID:20356846 PMID:21549626

    Open questions at the time
    • Physiological trigger that relieves CARD autoinhibition not defined
  11. 2011 Medium

    Identified a nuclear, transcription-regulatory role: cIAP1 binds the E2F1 DNA-binding domain at cell-cycle gene promoters to enhance proliferation.

    Evidence Co-IP, E2F1 reporter, ChIP on CCNE/CCNA, siRNA knockdown proliferation assay

    PMID:21653699

    Open questions at the time
    • Single lab
    • Did not initially establish a ubiquitin-based mechanism for E2F1 regulation
  12. 2013 High

    Established a stabilizing regulatory layer, showing OTUB1 removes K48 chains from cIAP1 within the TWEAK receptor complex to protect it from degradation.

    Evidence Co-IP, linkage-specific in vitro DUB assay, OTUB1 knockdown with pathway readouts, zebrafish validation

    PMID:23524849 PMID:33712742

    Open questions at the time
    • Balance between OTUB1, USP19 and HSP90β in setting steady-state cIAP1 levels not integrated
  13. 2017 Medium

    Resolved the molecular basis of cIAP1-driven transcription by showing K63-linked ubiquitination of E2F1 stabilizes it and licenses promoter binding during S phase and DNA damage.

    Evidence In vitro ubiquitination, K161R/K164R mutagenesis, ChIP on CCNE/TP73/APAF1, cell-cycle and DNA damage assays

    PMID:28542143

    Open questions at the time
    • Single lab
    • How nuclear versus cytoplasmic cIAP1 pools are partitioned to this function unclear
  14. 2019 High

    Defined the dominant in vivo physiological function by showing combined cIAP1/2 loss kills intestinal and hepatic tissue via caspase-8, rescued by Casp8/Ripk3 co-deletion.

    Evidence Conditional cIap1/2 double knockout mice, Casp8/Ripk3/Mlkl epistasis, cleaved caspase staining, NIK inhibition

    PMID:31141691

    Open questions at the time
    • Did not separate cIAP1-specific from cIAP2-specific roles in vivo
  15. 2022 High

    Detailed the degradation chemistry exploited by cIAP1-recruiting degraders, showing UBE2N-seeded K63 chains nucleate branched K48/K63 chains that recruit p97 and the proteasome.

    Evidence UBE2N knockout, in vitro E2 panel ubiquitination, MS linkage mapping, p97/UCH37/proteasome interaction assays

    PMID:36316570

    Open questions at the time
    • Whether this branched-chain logic governs cIAP1's endogenous substrates not established

Open questions

Synthesis pass · forward-looking unresolved questions
  • How the many cIAP1 activities—receptor-complex RIP ubiquitination, NIK degradation, caspase turnover, and nuclear E2F1/Mad1 regulation—are coordinated across subcellular compartments and which are physiologically dominant in specific tissues remains unresolved.
  • No unified model linking compartmental localization to substrate selection
  • Tissue-specific substrate hierarchy undefined
  • Most non-RIP1 substrates rest on single-lab evidence

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0016874 ligase activity 8 GO:0140096 catalytic activity, acting on a protein 6 GO:0031386 protein tag activity 3 GO:0098772 molecular function regulator activity 3
Localization
GO:0005634 nucleus 4 GO:0005829 cytosol 4 GO:0005886 plasma membrane 2 GO:0005783 endoplasmic reticulum 1 GO:0005794 Golgi apparatus 1
Pathway
R-HSA-162582 Signal Transduction 6 R-HSA-392499 Metabolism of proteins 4 R-HSA-5357801 Programmed Cell Death 4 R-HSA-1640170 Cell Cycle 3 R-HSA-168256 Immune System 3
Partners
E2F1NIKOTUB1RIPK1TRAF2TRAF3UBE2NUSP19
Complex memberships
LIGHT·LTβR complexTNF-R1 signaling complexTNF-R2 / TRAF2 complexTRAF2-TRAF3-NIK non-canonical NF-κB regulatory complex

Evidence

Reading pass · 57 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
1996 c-IAP1 is recruited to the TNF-R1 signaling complex via TRADD-mediated association with TRAF2, establishing its presence in TNF-R1 signaling independently of TNF-R2. Co-immunoprecipitation, TNF-dependent recruitment assay in cells Proceedings of the National Academy of Sciences of the United States of America High 8943045
1997 c-IAP1 and c-IAP2 bind specifically to caspases-3 and -7 via their BIR domains and inhibit their enzymatic activity in vitro (estimated Ki ≤0.1 µM), blocking caspase-3 processing in cell-free and intact cell systems. In vitro binding assay, in vitro caspase activity assay, cell-free cytochrome-c system, gene transfection overexpression The EMBO journal High 9384571
1998 NF-κB transcriptional activation induces expression of c-IAP1 and c-IAP2 (along with TRAF1 and TRAF2), and these proteins cooperatively suppress TNF-alpha-induced caspase-8 activation; c-IAP1/2 alone are sufficient to suppress etoposide-induced apoptosis. NF-κB inhibition/activation, gene transfection, caspase-8 activation assay, apoptosis assays Science (New York, N.Y.) High 9733516
2000 c-IAP1 is cleaved during apoptosis by caspase-3 to produce C-terminal fragments containing the RING domain; these fragments are proapoptotic, and the RING domain negatively regulates the antiapoptotic function of the N-terminal BIR domain. In vitro cleavage with purified caspase-3, transfection of deletion mutants, apoptosis assays The Journal of biological chemistry High 11106668
2002 c-IAP1 functions as an E3 ubiquitin ligase that ubiquitinates TRAF2 (but not TRAF1 despite binding both) downstream of TNF-RII engagement, leading to proteasomal degradation of TRAF2; E3-defective c-IAP1 mutant blocks this degradation and inhibits apoptosis. In vitro ubiquitination assay, co-immunoprecipitation, E3-defective mutant expression, proteasome inhibition, primary cell studies Nature High 11907583
2003 cIAP1 is irreversibly cleaved (inactivated) during p53-dependent apoptosis by the serine protease HTRA2, which interacts directly with cIAP1; serine protease inhibitors that block cIAP1 cleavage inhibit p53-dependent apoptosis. Co-immunoprecipitation, serine protease inhibitor treatment, apoptosis assay, p53 induction Genes & development Medium 12569127
2004 c-IAP1 and c-IAP2 ubiquitinate RIP (RIP1) in vitro; expression of c-IAP1/2 decreases steady-state RIP levels in a proteasome-dependent manner, requiring the RING domain of c-IAP2. In vitro ubiquitination assay, proteasome inhibitor rescue, deletion mutant analysis FEBS letters Medium 15147886
2004 c-IAP1 translation is driven by an internal ribosome entry site (IRES) in its 5'-UTR, and IRES-mediated translation is stimulated by pro-apoptotic stimuli (etoposide, sodium arsenite) that inhibit cap-dependent translation. Dicistronic RNA constructs, in vitro translation, transfection in multiple cell lines, hairpin insertion, cap-independent translation assay RNA (New York, N.Y.) Medium 14970392
2004 cIAP1 and cIAP2 are nuclear-cytoplasmic shuttling proteins; their nuclear export is CRM1-dependent, and a leucine-rich NES in the BIR2-BIR3 linker region mediates nuclear export of cIAP1. TRAF2 retains cIAP1/2 in the cytoplasm and prevents nuclear translocation; TNFα treatment reduces TRAF2-mediated cytoplasmic retention. Leptomycin B treatment, site-directed mutagenesis of NES, co-expression with TRAF2, immunofluorescence, subcellular fractionation Experimental cell research High 15265700
2004 In hematopoietic cells undergoing differentiation, c-IAP1 translocates from the nucleus to the Golgi apparatus via a nuclear export signal (NES) located in the CARD domain, in a leptomycin B-sensitive, CRM1-dependent mechanism. Immunofluorescence, leptomycin B treatment, site-directed mutagenesis of CARD NES, phorbol ester differentiation model Blood High 15187025
2005 cIAP1 and cIAP2 BIR2 and BIR3 domains bind caspases-7 and -9 but do NOT inhibit caspase activity due to critical substitutions in caspase-inhibitory contact residues; substituting these residues with XIAP equivalents converts cIAP BIRs into tight caspase inhibitors. In vitro binding assay, fluorogenic caspase activity assay, domain mutagenesis The Journal of biological chemistry High 16339151
2005 c-IAP1 mediates posttranscriptional downregulation of c-IAP2 via E3 ubiquitin ligase-dependent ubiquitination and proteasomal degradation, potentiated by TRAF2 as an adaptor; c-IAP1-deficient mice show elevated c-IAP2 protein without increased c-IAP2 mRNA. c-IAP1 knockout mice, wild-type vs. E3-defective c-IAP1 transfection, Western blot, RT-PCR Molecular and cellular biology High 15798218
2005 cIAP1 localizes predominantly to the nucleus (unlike cytoplasmic XIAP); apoptotic stimuli induce nuclear export of cIAP1 in a caspase-dependent manner. During mitosis, cIAP1 is released to cytosol and reassociates with the midbody; it interacts with Survivin during mitosis. Overexpression of cIAP1 causes G2-M accumulation, cytokinesis defects, and polyploidy. Immunofluorescence microscopy, subcellular fractionation, caspase inhibitor treatment, stable overexpression, cell cycle analysis Cancer research Medium 15665297
2005 Upon TNF-R2 signaling, the c-IAP1/TRAF2 complex translocates to a Triton X-100-insoluble perinuclear ER compartment containing the E2 enzyme Ubc6; Ubc6 serves as a cognate E2 for c-IAP1's E3 activity and is required for TNF-R2-dependent TRAF2 ubiquitination and degradation. Subcellular fractionation, confocal microscopy, co-immunoprecipitation, in vitro ubiquitination with Ubc6, dominant-negative Ubc6 mutant The EMBO journal High 15861135
2004 Smac/DIABLO selectively promotes rapid degradation of c-IAP1 and c-IAP2 (but not XIAP or Livin) by stimulating their auto-ubiquitination via its N-terminal IAP-binding motif binding to the BIR domains; ubiquitin-conjugating enzymes UbcH5a and UbcH6 are required for this ubiquitination. In vitro auto-ubiquitination assay, deletion mutants, N-terminal Smac peptide, proteasome inhibition, Western blot The Journal of biological chemistry High 14960576
2007 c-IAP1 functions as the E3 ubiquitin ligase for ASK1 downstream of TNFR2 signaling, leading to ASK1 ubiquitination and proteasomal degradation; c-IAP1 knockout primary B cells lack TNFR2-induced TRAF2 and ASK1 degradation and show prolonged p38 and JNK activation. Primary c-IAP1 knockout B cells, ubiquitination assay, proteasome inhibitor, kinase activity assay The Journal of biological chemistry High 17220297
2007 Birc2 (cIAP1) positively regulates formation of the TNF receptor complex I in endothelial cells, promoting NF-κB activation and maintaining vascular integrity; loss of Birc2 in zebrafish causes caspase-8-dependent apoptosis and vessel regression. Zebrafish forward genetic screen, null mutant analysis, genetic epistasis with NF-κB pathway, caspase-8 assay Nature genetics High 17934460
2007 c-IAP1 acts as an E3 ubiquitin ligase for Mad1 (MAX dimerization protein 1), promoting its proteasomal degradation, which cooperates with Myc to promote cell proliferation. In vitro ubiquitination assay, proteasome inhibitor, overexpression/knockdown proliferation assay Molecular cell Medium 18082613
2008 cIAP1 and cIAP2 promote cancer cell survival by functioning as E3 ubiquitin ligases that maintain constitutive K63-linked ubiquitination of RIP1; ubiquitinated RIP1 associates with pro-survival TAK1, while deubiquitinated RIP1 binds caspase-8 and induces apoptosis. IAP antagonist AEG40730 treatment, in vitro ubiquitination with purified components, co-immunoprecipitation of RIP1-TAK1 and RIP1-caspase-8 complexes Molecular cell High 18570872
2008 cIAP1 and cIAP2 are required for TNFα-stimulated RIP1 K63-linked polyubiquitination and downstream NF-κB activation; in vitro reconstitution with purified c-IAP1 and UbcH5a demonstrates direct K63-linked chain polymerization on RIP1. Genetic knockout cells, siRNA knockdown, IAP antagonist, in vitro ubiquitination reconstitution with purified cIAP1+UbcH5a The Journal of biological chemistry High 18621737
2008 Both cIAP1 and cIAP2 are required (redundantly) for TNFα-induced RIP1 polyubiquitination and NF-κB activation; combined loss of both cIAPs attenuates IKKβ phosphorylation and sensitizes cells to TNFα-mediated apoptosis. Combined genetic deletion and siRNA knockdown, TNF receptor complex immunoprecipitation, RIP1 ubiquitination assay, NF-κB activation assay Proceedings of the National Academy of Sciences of the United States of America High 18697935
2008 Noncanonical NF-κB activation is suppressed by a regulatory complex in which TRAF2 recruits cIAP1/2 and TRAF3 recruits NIK; cIAP1 and cIAP2 mediate proteasomal degradation of NIK within this complex, and combined inhibition of both cIAPs is required for noncanonical NF-κB activation. Complex assembly assay, cIAP inhibition (genetic and pharmacological), NIK degradation assay, primary B lymphocyte survival/proliferation assay Nature immunology High 18997794
2008 TWEAK/FN14 signaling promotes lysosomal (not proteasomal) degradation of the cIAP1-TRAF2 complex in a cIAP1-dependent manner, leading to noncanonical NF-κB activation and sensitization to TNFα-induced death. Lysosomal inhibitor vs. proteasomal inhibitor treatment, co-immunoprecipitation of FN14-cIAP1-TRAF2 complex, cIAP1 overexpression rescue The Journal of cell biology High 18606850
2008 Small molecules (ME-BS class) directly interact with the BIR3 domain of cIAP1, promote RING domain-dependent auto-ubiquitylation, and facilitate proteasomal degradation of cIAP1 selectively (not XIAP or cIAP2), sensitizing cancer cells to apoptosis. Direct binding assay (BIR3 domain), auto-ubiquitylation assay, proteasome inhibitor rescue, Western blot, apoptosis assay The Journal of biological chemistry Medium 18230607
2008 The CARD domain of cIAP1 contains a functional NES mediating CRM1-dependent nuclear export; the RING domain of cIAP1 degrades RING-bearing IAPs (cIAP1, cIAP2, XIAP, Livin) by ubiquitin-dependent and ubiquitin-independent proteasomal pathways. CARD NES mutagenesis, leptomycin B treatment, ubiquitination-deficient E1 mutant cells, cIAP1 RING domain transfection, proteasome inhibitor Molecular biology of the cell Medium 18434593
2008 During monocyte-to-macrophage differentiation, cIAP1 (after translocating from nucleus to cytoplasm) mediates proteasomal degradation of TRAF2 via its E3 ligase activity; TRAF2 is initially required for NF-κB activation during differentiation, and its subsequent cIAP1-mediated degradation is required for full macrophage function including cytokine secretion. cIAP1 inhibitor, TRAF2 siRNA knockdown, TRAF2 overexpression, NF-κB assay, cytokine measurement Blood Medium 18827186
2009 cIAP1 binds caspase-3 and caspase-7 at distinct steps of their processing via different mechanisms: it binds mature caspase-7 via its exposed IAP-binding motif AKPD, and binds partially processed caspase-3 via a prodomain-dependent non-classical mechanism. cIAP1 ubiquitinates both caspases via UbcH5 subfamily E2s (and UbcH8 for caspase-3), leading to their proteasomal degradation without directly inhibiting their enzymatic activity. In vitro binding assay, fluorogenic substrate assay, ubiquitination assay, chimeric caspase-3 with AKPD motif, proteasome inhibitor, UbcH5/UbcH8 identification The Journal of biological chemistry High 19258326
2009 cIAP1 mediates NEMO monoubiquitination in response to genotoxic stress as part of NF-κB activation; cIAP1, cIAP2, and XIAP act cooperatively and non-redundantly at distinct steps: XIAP activates TAK1, cIAP1 ubiquitinates NEMO, and cIAP2 acts downstream of NEMO ubiquitination. Genotoxic agents (camptothecin, etoposide, doxorubicin), siRNA knockdown of individual IAPs, NEMO ubiquitination assay, NF-κB activation assay Cancer research Medium 19223549
2009 A UBA (ubiquitin-associated) domain in cIAP1 located between the BIR domains and the CARD/RING domains binds mono-ubiquitin and K48- and K63-linked polyubiquitin chains; UBA domain mutations abrogate ubiquitin binding and decrease IAP antagonist-stimulated proteasomal degradation of cIAP1. Surface plasmon resonance, isothermal titration calorimetry, NMR analysis of UBA-ubiquitin interaction, UBA domain point mutagenesis, proteasome degradation assay The Biochemical journal High 18939944
2009 cIAP1 and cIAP2 are required for NOD1- and NOD2-mediated innate immune signaling; they function as E3 ubiquitin ligases for RIP2 ubiquitination, and their deficiency impairs cytokine/chemokine production in macrophages and colonocytes in vitro and in vivo. Birc2−/− and Birc3−/− mouse macrophages, RNAi in colonocytes, RIP2 ubiquitination assay, in vivo NOD agonist challenge, colitis model Immunity High 19464198
2010 c-IAP1 and UbcH5 family E2 enzymes promote K11-linked polyubiquitination of RIP1 in vitro and in vivo within the TNFR1 signaling complex; TNFα-stimulated NF-κB activation involves endogenous K11-linked ubiquitination of RIP1 in a c-IAP1- and UbcH5-dependent manner. NEMO efficiently binds K11-linked ubiquitin chains. Directed yeast two-hybrid screen for E2 partners, in vitro ubiquitination with purified components, mass spectrometry of ubiquitin linkage, UbcH5 siRNA knockdown, TNFR1 complex immunoprecipitation The EMBO journal High 21113135
2010 cIAP1 promotes cell survival against TNF-induced necrosis by maintaining RIP1 ubiquitination, which prevents RIP1 kinase activation, RIP1/RIP3 necrosome formation, and ROS accumulation; depletion of cIAP1 (but not cIAP2) is specifically responsible for sensitization to TNF-induced necrosis. RNAi (individual IAP knockdown), IAP antagonist BV6, RIP1 kinase inhibitor, RIP3 knockdown, CYLD knockdown, ROS measurement, cell death assay Cell death and differentiation High 21052097
2010 RIPK1 promotes cell survival in TNF-stimulated cells by stabilizing TRAF2 and cIAP1; in RIPK1-deficient cells, TNF stimulation causes rapid proteasomal degradation of TRAF2 and cIAP1, leading to NIK accumulation, non-canonical NF-κB activation, reduction of cFLIPL, and caspase-8 activation. RIPK1−/− cells, TNF stimulation time course, proteasome inhibitor, Western blot for TRAF2/cIAP1/NIK/cFLIPL The Journal of biological chemistry Medium 21339290
2010 The RING domain of cIAP1 requires dimerization and E2 binding for IAP antagonist-induced auto-degradation and for TNF-induced NF-κB activation and prevention of non-canonical NF-κB; RING mutants unable to dimerize or bind E2 fail these functions. cIAP-deleted cells reconstituted with RING point mutants (dimerization-defective, E2-binding-defective), TNF stimulation, IAP antagonist treatment, NF-κB assays The Journal of biological chemistry High 20356846
2011 The CARD domain of cIAP1 autoinhibits its E3 ligase activity by preventing RING dimerization, E2 binding, and E2 activation; CARD-mediated autoregulation suppresses cell proliferation and migration, maximally suppresses caspase-8-dependent apoptosis, and prevents vascular degeneration in vivo. Crystal structure of CARD domain, RING dimerization assay, E2 activation assay, CARD deletion/mutation, cell proliferation/migration assay, zebrafish vascular assay Molecular cell High 21549626
2011 cIAP1 and cIAP2 are direct E3 ubiquitin ligases for RIP1, RIP2, RIP3, and RIP4; cIAP1 conjugates diverse ubiquitin chain types including linear chains to these substrates. K63-linked ubiquitination of RIP4 on Lys51 and Lys145 by cIAP1 is required for NF-κB activation. Co-immunoprecipitation (direct binding), in vitro ubiquitination assay with purified components, RIP4 K51R/K145R mutagenesis, NF-κB reporter assay PloS one High 21931591
2011 cIAP1 and cIAP2 are required for efficient caspase-1 activation by the inflammasome; they interact with caspase-1-containing complexes via TRAF2 and mediate non-degradative K63-linked polyubiquitination of caspase-1; deficiency in Birc2 or Birc3 impairs caspase-1 activation and inflammasome responses in vivo. Birc2−/− and Birc3−/− mouse macrophages, co-immunoprecipitation, K63-ubiquitination assay, in vivo peritonitis model, caspase-1 activity assay Immunity High 22195745
2011 Smac mimetic-induced degradation of cIAP1 requires its binding to TRAF2; degradation of cIAP2 requires the presence of cIAP1 and cIAP2 RING finger dimerization and E2 binding. cIAP2-MALT1 oncofusion (lacking the RING) is resistant to Smac mimetics. TRAF2-binding mutants, cIAP1/2 double-knockout cells, RING mutants, cIAP2-MALT1 expression, Western blot Cell death and differentiation Medium 21331077
2011 USP19 deubiquitinase interacts with c-IAP1 and c-IAP2, and stabilizes c-IAP levels primarily through deubiquitinase-independent mechanisms in vivo; knockdown of USP19 decreases c-IAP levels and enhances TNFα-induced caspase activation and apoptosis in a c-IAP1/2-dependent manner. Co-immunoprecipitation, in vitro deubiquitination assay, USP19 knockdown, overexpression, caspase activity assay The Journal of biological chemistry Medium 21849505
2011 Nuclear cIAP1 directly interacts with the DNA-binding domain of E2F1 transcription factor, increases E2F1 transcriptional activity on CCNE and CCNA promoters, and is recruited to E2F1 binding sites by chromatin immunoprecipitation; cIAP1 silencing inhibits cyclin E/A expression and cell proliferation. Co-immunoprecipitation, E2F1 transcription reporter assay, chromatin immunoprecipitation (ChIP), cIAP1 siRNA knockdown, cell proliferation assay The Journal of biological chemistry Medium 21653699
2012 cIAP1 limits macrophage necroptosis by suppressing RIP3 (and to a lesser extent RIP1) expression via post-transcriptional mechanisms, preventing necrosome formation; specific cIAP1 knockout causes elevated macrophage cell death and compromised control of Listeria monocytogenes. SMAC mimetic treatment, RNAi individual knockdown, RIP1 kinase inhibitor, RIP3 knockdown, single cIAP1 or cIAP2 knockout macrophages, in vivo Listeria model Cell death and differentiation Medium 22576661
2012 Loss of cIAP1 activates the noncanonical NF-κB pathway (via NIK/p100/RelB), which promotes myoblast fusion; TWEAK at low concentrations activates this pathway to increase myoblast fusion without causing atrophy. cIAP1-null cells, siRNA knockdown of p100/RelB/IKKα/NIK, TWEAK treatment, myoblast fusion quantification Science signaling Medium 23074266
2013 OTUB1 deubiquitinase associates with c-IAP1, disassembles K48-linked polyubiquitin chains from c-IAP1 in vitro and in vivo within the TWEAK receptor signaling complex, thereby stabilizing c-IAP1; OTUB1 knockdown promotes c-IAP1 degradation, caspase activation, and reduces TWEAK-induced NF-κB and MAPK signaling. Co-immunoprecipitation, in vitro deubiquitination assay (K48-linkage specific), OTUB1 siRNA, cell death assay, NF-κB/MAPK reporter, zebrafish OTUB1 suppression The EMBO journal High 23524849
2015 BIRC2 (cIAP1) functions as a negative regulator of noncanonical NF-κB-dependent HIV-1 LTR transcription; depletion of BIRC2 by Smac mimetics activates HIV-1 transcription and reverses latency, synergizing with HDACi panobinostat in patient-derived CD4+ T cells. RNAi screen, BIRC2 siRNA knockdown, Smac mimetic treatment, HIV-1 LTR reporter, latency reversal assay in JLat cells and primary CD4+ T cells from ART-suppressed patients Cell host & microbe Medium 26355217
2017 cIAP1 E3 ubiquitin ligase promotes K63-linked polyubiquitination of E2F1 on lysine residues 161/164, which stabilizes E2F1 and increases its transcriptional activity; this modification is required for E2F1 binding to CCNE, TP73 and APAF1 promoters and for E2F1 stabilization in response to DNA damage (etoposide) and during S phase. In vitro ubiquitination assay, K161R/K164R E2F1 mutagenesis, ChIP on CCNE/TP73/APAF1 promoters, cell cycle synchronization, DNA damage assay Cell death & disease Medium 28542143
2017 TLR-MyD88 signaling causes proteasomal degradation of cIAP1 and TRAF2 by inducing TNF and TNFR2 signaling; myeloid-specific cIAP1 loss in XIAP-deficient cells promotes TLR-induced RIPK3-caspase-8 activation and IL-1β production; TNFR2 deletion limits cIAP1-TRAF2 degradation and cell death. Myeloid-specific cIAP1 conditional knockout, TNFR2 deletion, TLR ligand stimulation, caspase-8 activation assay, IL-1β measurement, Western blot for cIAP1/TRAF2 Cell reports High 28723569
2018 S-nitrosylation of cIAP1 on cysteines 571 and 574 by NO donor GTN inhibits its E3 ubiquitin ligase activity, reducing K63-linked ubiquitination of RIP1 and triggering assembly of a death complex, converting TNFα from a pro-survival to a pro-death signal. S-nitrosylation site identification (Cys571/574), E3 ligase activity assay after S-nitrosylation, RIP1 ubiquitination assay, death complex co-immunoprecipitation, cell death assay Cancer research Medium 29431638
2018 cIAP1 is recruited to the TNFR2 signaling complex and mediates K63-linked polyubiquitination; cIAP1 recruitment to TNFR2 is required for HOIP (LUBAC) recruitment and M1-ubiquitination at the TNFR2 complex; both HOIP and cIAP1 are required for TNFR2-induced canonical NF-κB activation. TNFR2 signaling complex immunoprecipitation, cIAP antagonist treatment, ubiquitin linkage analysis, HOIP recruitment assay, NF-κB activation assay Biochemical pharmacology Medium 29378181
2019 Combined loss of cIAP1 and cIAP2 in adult mice causes rapid intestinal and hepatic cell death involving caspase-8 and caspase-3 cleavage; deletion of Casp8 and Ripk3 together (but not Ripk3 alone) prevents cell death and prolongs survival, indicating the primary function is suppression of caspase-8-dependent death. Residual inflammation is reduced by NIK inhibition. Conditional cIap1/2 double knockout in adult mice, Casp8/Ripk3/Mlkl genetic deletion epistasis, cleaved caspase immunostaining, NIK inhibition Cell reports High 31141691
2020 Structural and biophysical studies of cIAP1 BIR3 domain in ternary complexes with BTK and heterobifunctional degraders (PROTACs) reveal that increased ternary complex stability or rigidity does not necessarily correlate with increased degradation efficiency. Biochemical binding assays, biophysical measurements, crystal structure of ternary complex (BTK-degrader-cIAP1) Nature chemical biology High 33199914
2021 OTUB1 prevents K48-linked polyubiquitination and degradation of c-IAP1 in hepatocytes; OTUB1 deficiency leads to c-IAP1 degradation, reduced K63-linked polyubiquitination of RIPK1, increased RIPK1 phosphorylation and necrosome formation, and lethal necroptosis in bacterial and sterile liver inflammation. Hepatocyte-specific OTUB1 knockout mice, OTUB1-deficient HepG2 cells, RIPK1 inhibitor necrostatin-1s, MLKL knockout epistasis, K48/K63 ubiquitin linkage assays, Listeria/DGal-TNF challenge Cell death and differentiation High 33712742
2022 cIAP1-targeting degraders (SNIPERs/PROTACs) require the K63-specific E2 enzyme UBE2N for efficient target protein degradation; UBE2N-catalyzed K63-linked chains facilitate assembly of branched K48/K63 and K11/K48 ubiquitin chains on substrates, recruiting p97/VCP, UCH37, and the proteasome for degradation. UBE2N siRNA/knockout, in vitro ubiquitination with E2 panel, mass spectrometry of ubiquitin chain linkages, p97/UCH37/proteasome interaction assays Nature chemical biology High 36316570
2008 HSP90β acts as a chaperone for c-IAP1; HSP90β inhibition or siRNA depletion induces c-IAP1 auto-ubiquitination and proteasomal degradation, and prevents cell differentiation; specific depletion of c-IAP1 alone is sufficient to inhibit cell differentiation. HSP90 inhibitor treatment, HSP90α/β-specific siRNA, co-immunoprecipitation, auto-ubiquitination assay, proteasome inhibitor rescue, differentiation assay Cell death and differentiation Medium 18239673
2014 cIAP1 conjugates predominantly K63-linked ubiquitin chains to MEKK2 and MEKK3, which impedes their interaction with MEK5 in a trimeric complex, leading to ERK5 inactivation; loss of cIAP1 causes hyperactivation of ERK5 and promotes skeletal myoblast differentiation. Co-immunoprecipitation, in vitro ubiquitination assay, K63-ubiquitin linkage analysis, MEKK2/3-MEK5 interaction assay, ERK5 activation assay, myoblast differentiation model The EMBO journal High 24975362
2006 F-box protein Fbxo7 interacts with cIAP1 in human cells and promotes cIAP1 ubiquitination; they co-localize in cytoplasm, nucleus, and Golgi-like structures when co-expressed. Yeast two-hybrid screen, co-immunoprecipitation, co-localization by microscopy, ubiquitination assay Biochemical and biophysical research communications Low 16510124
2011 cIAP1 promotes SNIPER-4-mediated ubiquitination and proteasomal degradation of CRABP-II when crosslinked to cIAP1 by a hybrid small molecule; this establishes cIAP1 as a recruitable E3 ligase for targeted protein degradation of neo-substrates. SNIPER hybrid molecule, Western blot of CRABP-II degradation, proteasome inhibitor rescue, ubiquitination assay FEBS letters Medium 21414315
2003 cIAP1 is a component of the endogenous LIGHT·LTβR complex, associating with TRAF2, TRAF3, and Smac at the lymphotoxin-beta receptor; its presence with Smac reveals a mechanism for LIGHT/LTβR-induced apoptosis. Affinity purification of endogenous LIGHT·LTβR complex, mass spectrometry identification, co-immunoprecipitation confirmation in U937 and HEK293 cells The Journal of biological chemistry Medium 12571250

Source papers

Stage 0 corpus · 100 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
1998 NF-kappaB antiapoptosis: induction of TRAF1 and TRAF2 and c-IAP1 and c-IAP2 to suppress caspase-8 activation. Science (New York, N.Y.) 2440 9733516
1997 The c-IAP-1 and c-IAP-2 proteins are direct inhibitors of specific caspases. The EMBO journal 1060 9384571
2008 cIAP1 and cIAP2 facilitate cancer cell survival by functioning as E3 ligases that promote RIP1 ubiquitination. Molecular cell 933 18570872
2008 Noncanonical NF-kappaB activation requires coordinated assembly of a regulatory complex of the adaptors cIAP1, cIAP2, TRAF2 and TRAF3 and the kinase NIK. Nature immunology 524 18997794
2008 c-IAP1 and c-IAP2 are critical mediators of tumor necrosis factor alpha (TNFalpha)-induced NF-kappaB activation. The Journal of biological chemistry 465 18621737
2008 Both cIAP1 and cIAP2 regulate TNFalpha-mediated NF-kappaB activation. Proceedings of the National Academy of Sciences of the United States of America 453 18697935
2002 TNF-RII and c-IAP1 mediate ubiquitination and degradation of TRAF2. Nature 389 11907583
1996 The tumor necrosis factor receptor 2 signal transducers TRAF2 and c-IAP1 are components of the tumor necrosis factor receptor 1 signaling complex. Proceedings of the National Academy of Sciences of the United States of America 376 8943045
2005 The human anti-apoptotic proteins cIAP1 and cIAP2 bind but do not inhibit caspases. The Journal of biological chemistry 301 16339151
2010 c-IAP1 and UbcH5 promote K11-linked polyubiquitination of RIP1 in TNF signalling. The EMBO journal 297 21113135
2010 cIAP1 and TAK1 protect cells from TNF-induced necrosis by preventing RIP1/RIP3-dependent reactive oxygen species production. Cell death and differentiation 290 21052097
2009 Cellular inhibitors of apoptosis cIAP1 and cIAP2 are required for innate immunity signaling by the pattern recognition receptors NOD1 and NOD2. Immunity 287 19464198
2013 RIPK3 contributes to TNFR1-mediated RIPK1 kinase-dependent apoptosis in conditions of cIAP1/2 depletion or TAK1 kinase inhibition. Cell death and differentiation 265 23892367
2008 TWEAK-FN14 signaling induces lysosomal degradation of a cIAP1-TRAF2 complex to sensitize tumor cells to TNFalpha. The Journal of cell biology 224 18606850
2001 Identification of cIAP1 as a candidate target gene within an amplicon at 11q22 in esophageal squamous cell carcinomas. Cancer research 171 11559525
2004 Smac/DIABLO selectively reduces the levels of c-IAP1 and c-IAP2 but not that of XIAP and livin in HeLa cells. The Journal of biological chemistry 167 14960576
2005 Posttranscriptional downregulation of c-IAP2 by the ubiquitin protein ligase c-IAP1 in vivo. Molecular and cellular biology 162 15798218
2011 Cellular inhibitors of apoptosis proteins cIAP1 and cIAP2 are required for efficient caspase-1 activation by the inflammasome. Immunity 143 22195745
2008 Small molecules destabilize cIAP1 by activating auto-ubiquitylation. The Journal of biological chemistry 137 18230607
2009 The E3 ubiquitin ligase cIAP1 binds and ubiquitinates caspase-3 and -7 via unique mechanisms at distinct steps in their processing. The Journal of biological chemistry 134 19258326
2003 A comprehensive search for DNA amplification in lung cancer identifies inhibitors of apoptosis cIAP1 and cIAP2 as candidate oncogenes. Human molecular genetics 133 12651874
2012 cIAP1 and cIAP2 limit macrophage necroptosis by inhibiting Rip1 and Rip3 activation. Cell death and differentiation 130 22576661
2002 Expression of cIAP1, a target for 11q22 amplification, correlates with resistance of cervical cancers to radiotherapy. Cancer research 130 12208731
2015 BIRC2/cIAP1 Is a Negative Regulator of HIV-1 Transcription and Can Be Targeted by Smac Mimetics to Promote Reversal of Viral Latency. Cell host & microbe 124 26355217
2017 XIAP Loss Triggers RIPK3- and Caspase-8-Driven IL-1β Activation and Cell Death as a Consequence of TLR-MyD88-Induced cIAP1-TRAF2 Degradation. Cell reports 120 28723569
2007 Birc2 (cIap1) regulates endothelial cell integrity and blood vessel homeostasis. Nature genetics 119 17934460
2004 Receptor interacting protein is ubiquitinated by cellular inhibitor of apoptosis proteins (c-IAP1 and c-IAP2) in vitro. FEBS letters 117 15147886
2013 OTUB1 modulates c-IAP1 stability to regulate signalling pathways. The EMBO journal 102 23524849
2011 Specific degradation of CRABP-II via cIAP1-mediated ubiquitylation induced by hybrid molecules that crosslink cIAP1 and the target protein. FEBS letters 96 21414315
2011 cIAP1/2 are direct E3 ligases conjugating diverse types of ubiquitin chains to receptor interacting proteins kinases 1 to 4 (RIP1-4). PloS one 96 21931591
2009 Ubiquitin binding modulates IAP antagonist-stimulated proteasomal degradation of c-IAP1 and c-IAP2(1). The Biochemical journal 95 18939944
2000 c-IAP1 is cleaved by caspases to produce a proapoptotic C-terminal fragment. The Journal of biological chemistry 95 11106668
2005 cIAP1 Localizes to the nuclear compartment and modulates the cell cycle. Cancer research 94 15665297
2011 Deletion of cIAP1 and cIAP2 in murine B lymphocytes constitutively activates cell survival pathways and inactivates the germinal center response. Blood 91 21300983
2011 Molecular determinants of Smac mimetic induced degradation of cIAP1 and cIAP2. Cell death and differentiation 89 21331077
2020 Snapshots and ensembles of BTK and cIAP1 protein degrader ternary complexes. Nature chemical biology 88 33199914
2009 cIAP1, cIAP2, and XIAP act cooperatively via nonredundant pathways to regulate genotoxic stress-induced nuclear factor-kappaB activation. Cancer research 88 19223549
2005 TNF-alpha induced c-IAP1/TRAF2 complex translocation to a Ubc6-containing compartment and TRAF2 ubiquitination. The EMBO journal 88 15861135
2011 CARD-mediated autoinhibition of cIAP1's E3 ligase activity suppresses cell proliferation and migration. Molecular cell 87 21549626
2011 In TNF-stimulated cells, RIPK1 promotes cell survival by stabilizing TRAF2 and cIAP1, which limits induction of non-canonical NF-kappaB and activation of caspase-8. The Journal of biological chemistry 85 21339290
2009 MMP13, Birc2 (cIAP1), and Birc3 (cIAP2), amplified on chromosome 9, collaborate with p53 deficiency in mouse osteosarcoma progression. Cancer research 84 19276372
2006 Altered expression of c-IAP1, survivin, and Smac contributes to chemotherapy resistance in thyroid cancer cells. Cancer research 82 16618750
2009 Connective tissue growth factor confers drug resistance in breast cancer through concomitant up-regulation of Bcl-xL and cIAP1. Cancer research 81 19351859
2011 The USP19 deubiquitinase regulates the stability of c-IAP1 and c-IAP2. The Journal of biological chemistry 77 21849505
2003 CIAP1 and the serine protease HTRA2 are involved in a novel p53-dependent apoptosis pathway in mammals. Genes & development 73 12569127
2012 TWEAK and cIAP1 regulate myoblast fusion through the noncanonical NF-κB signaling pathway. Science signaling 71 23074266
2007 Tumor necrosis factor receptor 2 signaling induces selective c-IAP1-dependent ASK1 ubiquitination and terminates mitogen-activated protein kinase signaling. The Journal of biological chemistry 71 17220297
2012 Double protein knockdown of cIAP1 and CRABP-II using a hybrid molecule consisting of ATRA and IAPs antagonist. Bioorganic & medicinal chemistry letters 66 22658364
2012 Critical role for antiapoptotic Bcl-xL and Mcl-1 in human macrophage survival and cellular IAP1/2 (cIAP1/2) in resistance to HIV-Vpr-induced apoptosis. The Journal of biological chemistry 65 22403404
2007 c-IAP1 cooperates with Myc by acting as a ubiquitin ligase for Mad1. Molecular cell 65 18082613
2016 SMAC Mimetic Birinapant plus Radiation Eradicates Human Head and Neck Cancers with Genomic Amplifications of Cell Death Genes FADD and BIRC2. Cancer research 61 27469115
2018 ASTX660, a Novel Non-peptidomimetic Antagonist of cIAP1/2 and XIAP, Potently Induces TNFα-Dependent Apoptosis in Cancer Cell Lines and Inhibits Tumor Growth. Molecular cancer therapeutics 59 29695633
2006 The F-box protein Fbxo7 interacts with human inhibitor of apoptosis protein cIAP1 and promotes cIAP1 ubiquitination. Biochemical and biophysical research communications 57 16510124
2019 Ubiquitin Ligases cIAP1 and cIAP2 Limit Cell Death to Prevent Inflammation. Cell reports 56 31141691
2016 LCL161 increases paclitaxel-induced apoptosis by degrading cIAP1 and cIAP2 in NSCLC. Journal of experimental & clinical cancer research : CR 55 27737687
2004 Translation of cellular inhibitor of apoptosis protein 1 (c-IAP1) mRNA is IRES mediated and regulated during cell stress. RNA (New York, N.Y.) 55 14970392
2008 The RING domain of cIAP1 mediates the degradation of RING-bearing inhibitor of apoptosis proteins by distinct pathways. Molecular biology of the cell 54 18434593
2018 Antagonist of cIAP1/2 and XIAP enhances anti-tumor immunity when combined with radiation and PD-1 blockade in a syngeneic model of head and neck cancer. Oncoimmunology 53 30393585
2016 Long non-coding RNA CRNDE promotes gallbladder carcinoma carcinogenesis and as a scaffold of DMBT1 and C-IAP1 complexes to activating PI3K-AKT pathway. Oncotarget 52 27637083
2012 Cyclic GMP/protein kinase G type-Iα (PKG-Iα) signaling pathway promotes CREB phosphorylation and maintains higher c-IAP1, livin, survivin, and Mcl-1 expression and the inhibition of PKG-Iα kinase activity synergizes with cisplatin in non-small cell lung cancer cells. Journal of cellular biochemistry 52 22740515
2004 Translocation of the inhibitor of apoptosis protein c-IAP1 from the nucleus to the Golgi in hematopoietic cells undergoing differentiation: a nuclear export signal-mediated event. Blood 51 15187025
2003 Endogenous association of TRAF2, TRAF3, cIAP1, and Smac with lymphotoxin beta receptor reveals a novel mechanism of apoptosis. The Journal of biological chemistry 51 12571250
2020 Lobaplatin induces pyroptosis through regulating cIAP1/2, Ripoptosome and ROS in nasopharyngeal carcinoma. Biochemical pharmacology 48 32413426
2015 XIAP and cIAP1 amplifications induce Beclin 1-dependent autophagy through NFκB activation. Human molecular genetics 48 25669656
2008 Interaction of heat-shock protein 90 beta isoform (HSP90 beta) with cellular inhibitor of apoptosis 1 (c-IAP1) is required for cell differentiation. Cell death and differentiation 48 18239673
2021 cIAP1/2 antagonism eliminates MHC class I-negative tumors through T cell-dependent reprogramming of mononuclear phagocytes. Science translational medicine 46 34011631
2012 An inactivating caspase 11 passenger mutation originating from the 129 murine strain in mice targeted for c-IAP1. The Biochemical journal 46 22332634
2014 Role of the TWEAK-Fn14-cIAP1-NF-κB Signaling Axis in the Regulation of Myogenesis and Muscle Homeostasis. Frontiers in immunology 45 24550918
2014 IGF2BP1 controls cell death and drug resistance in rhabdomyosarcomas by regulating translation of cIAP1. Oncogene 45 24704827
2014 Ceramide targets xIAP and cIAP1 to sensitize metastatic colon and breast cancer cells to apoptosis induction to suppress tumor progression. BMC cancer 44 24422988
2020 ASTX660, an antagonist of cIAP1/2 and XIAP, increases antigen processing machinery and can enhance radiation-induced immunogenic cell death in preclinical models of head and neck cancer. Oncoimmunology 43 32002309
2020 BIRC2 Expression Impairs Anti-Cancer Immunity and Immunotherapy Efficacy. Cell reports 41 32846130
2003 Akt activity in endometrial cancer cells: regulation of cell survival through cIAP-1. International journal of oncology 41 12888921
2010 Tumor necrosis factor (TNF) signaling, but not TWEAK (TNF-like weak inducer of apoptosis)-triggered cIAP1 (cellular inhibitor of apoptosis protein 1) degradation, requires cIAP1 RING dimerization and E2 binding. The Journal of biological chemistry 40 20356846
2021 OTUB1 prevents lethal hepatocyte necroptosis through stabilization of c-IAP1 during murine liver inflammation. Cell death and differentiation 39 33712742
2008 cIAP1-dependent TRAF2 degradation regulates the differentiation of monocytes into macrophages and their response to CD40 ligand. Blood 39 18827186
2012 Gene network revealed involvements of Birc2, Birc3 and Tnfrsf1a in anti-apoptosis of injured peripheral nerves. PloS one 38 23028454
2011 Cellular inhibitor of apoptosis protein-1 (cIAP1) can regulate E2F1 transcription factor-mediated control of cyclin transcription. The Journal of biological chemistry 38 21653699
2020 Dual Targeting of the p38 MAPK-HO-1 Axis and cIAP1/XIAP by Demethoxycurcumin Triggers Caspase-Mediated Apoptotic Cell Death in Oral Squamous Cell Carcinoma Cells. Cancers 36 32188144
2010 Rb inactivation accelerates neoplastic growth and substitutes for recurrent amplification of cIAP1, cIAP2 and Yap1 in sporadic mammary carcinoma associated with p53 deficiency. Oncogene 36 20676140
2018 The E3 ubiquitin ligases HOIP and cIAP1 are recruited to the TNFR2 signaling complex and mediate TNFR2-induced canonical NF-κB signaling. Biochemical pharmacology 35 29378181
2005 Expression of C-IAP1, C-IAP2 and SURVIVIN discriminates different types of lymphoid malignancies. British journal of haematology 35 16156855
2004 Nuclear shuttling and TRAF2-mediated retention in the cytoplasm regulate the subcellular localization of cIAP1 and cIAP2. Experimental cell research 35 15265700
2022 cIAP1-based degraders induce degradation via branched ubiquitin architectures. Nature chemical biology 34 36316570
2018 S-Nitrosylation of cIAP1 Switches Cancer Cell Fate from TNFα/TNFR1-Mediated Cell Survival to Cell Death. Cancer research 34 29431638
2018 Inhibitor of apoptosis proteins, NAIP, cIAP1 and cIAP2 expression during macrophage differentiation and M1/M2 polarization. PloS one 34 29518103
2015 MicroRNA-29c Correlates with Neuroprotection Induced by FNS by Targeting Both Birc2 and Bak1 in Rat Brain after Stroke. CNS neuroscience & therapeutics 34 25678279
2021 Targeting c-IAP1, c-IAP2, and Bcl-2 Eliminates Senescent Glioblastoma Cells Following Temozolomide Treatment. Cancers 33 34298797
2014 Potent and selective small-molecule inhibitors of cIAP1/2 proteins reveal that the binding of Smac mimetics to XIAP BIR3 is not required for their effective induction of cell death in tumor cells. ACS chemical biology 33 24521431
2000 p21WAF1 prevents down-modulation of the apoptotic inhibitor protein c-IAP1 and inhibits leukemic apoptosis. Molecular medicine (Cambridge, Mass.) 33 11071269
2015 IRF-1 inhibits NF-κB activity, suppresses TRAF2 and cIAP1 and induces breast cancer cell specific growth inhibition. Cancer biology & therapy 31 26011589
2010 Lipopolysaccharide induces autophagy through BIRC2 in human umbilical vein endothelial cells. Journal of cellular physiology 30 20458734
2022 TRIM56 promotes malignant progression of glioblastoma by stabilizing cIAP1 protein. Journal of experimental & clinical cancer research : CR 29 36471347
2015 Oncogenic activity of BIRC2 and BIRC3 mutants independent of nuclear factor-κB-activating potential. Cancer science 29 26094954
2009 Identification of ARIA regulating endothelial apoptosis and angiogenesis by modulating proteasomal degradation of cIAP-1 and cIAP-2. Proceedings of the National Academy of Sciences of the United States of America 28 19416853
2021 Shikonin promotes ubiquitination and degradation of cIAP1/2-mediated apoptosis and necrosis in triple negative breast cancer cells. Chinese medicine 27 33526051
2019 Targeted ablation of the cellular inhibitor of apoptosis 1 (cIAP1) attenuates denervation-induced skeletal muscle atrophy. Skeletal muscle 27 31126323
2014 Ubiquitin-dependent regulation of MEKK2/3-MEK5-ERK5 signaling module by XIAP and cIAP1. The EMBO journal 27 24975362
2006 Chenodeoxycholic acid and taurochenodexycholic acid induce anti-apoptotic cIAP-1 expression in human hepatocytes. Journal of gastroenterology and hepatology 26 17074018
2017 DNA damage and S phase-dependent E2F1 stabilization requires the cIAP1 E3-ubiquitin ligase and is associated with K63-poly-ubiquitination on lysine 161/164 residues. Cell death & disease 25 28542143

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