Affinage

BIRC2

Baculoviral IAP repeat-containing protein 2 · UniProt Q13490

Length
618 aa
Mass
69.9 kDa
Annotated
2026-04-28
100 papers in source corpus 55 papers cited in narrative 55 extracted findings

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

BIRC2 (cIAP1) is a RING-domain E3 ubiquitin ligase that serves as a central regulator of TNF receptor superfamily signaling, NF-κB activation, and programmed cell death. Its E3 ligase activity is held in check by intramolecular autoinhibition: BIR domains suppress RING dimerization and the CARD domain further restrains E2 engagement, until Smac/DIABLO or IAP-antagonist binding relieves this inhibition, enabling RING dimerization, substrate ubiquitination, and autoubiquitination (PMID:22021857, PMID:21393245, PMID:21549626). cIAP1 ubiquitinates RIP1 with K11- and K63-linked chains within the TNFR1 signalosome to sustain canonical NF-κB signaling and suppress caspase-8-dependent apoptosis and RIP1/RIP3-dependent necroptosis; it similarly ubiquitinates RIP2 to transduce NOD1/NOD2 innate immune signals, K63-ubiquitinates caspase-1 to facilitate inflammasome activation, and targets NIK for degradation to restrain noncanonical NF-κB (PMID:18570872, PMID:21113135, PMID:19464198, PMID:22195745, PMID:25246529). Beyond death-receptor signaling, cIAP1 ubiquitinates TRAF2, Mad1, E2F1, MEKK2/3, and IKKε to regulate macrophage differentiation, Myc-dependent proliferation, cell-cycle gene transcription, ERK5 signaling, and DNA-damage responses (PMID:11907583, PMID:18082613, PMID:28542143, PMID:24975362, PMID:23453969).

Mechanistic history

Synthesis pass · year-by-year structured walk · 14 steps
  1. 1997 High

    The initial question of how IAP-family proteins suppress apoptosis was addressed by showing cIAP1 directly binds caspases-3 and -7 via BIR domains and inhibits their activity in vitro, establishing cIAP1 as a direct caspase inhibitor.

    Evidence In vitro pulldown and fluorogenic caspase activity assays with purified proteins

    PMID:9384571

    Open questions at the time
    • Later work showed cIAP1 BIR domains lack key residues for tight caspase inhibition, questioning physiological relevance of direct inhibition
    • Relative contribution of caspase binding vs. ubiquitination to anti-apoptotic function unresolved
  2. 1998 High

    The question of how NF-κB suppresses TNF-induced apoptosis was answered by identifying cIAP1 as a direct NF-κB transcriptional target that cooperates with TRAF1/TRAF2 to suppress caspase-8 activation, placing cIAP1 within a feed-forward survival circuit.

    Evidence Reporter assays, dominant-negative NF-κB, TNF-α/etoposide apoptosis assays

    PMID:9733516

    Open questions at the time
    • Mechanism by which cIAP1 suppresses caspase-8 not yet defined at this point
  3. 2002 High

    cIAP1 was established as an E3 ubiquitin ligase, resolving the question of its enzymatic function: it ubiquitinates TRAF2 in a RING-dependent manner for proteasomal degradation upon TNF-RII engagement.

    Evidence In vitro ubiquitination assay, RING-domain mutant analysis, proteasome inhibitor rescue

    PMID:11907583

    Open questions at the time
    • E2 enzyme specificity not defined
    • Whether E3 activity extends to other substrates unknown
  4. 2004 High

    The substrate repertoire and subcellular dynamics of cIAP1 were expanded: cIAP1 directly ubiquitinates RIP1, Smac enhances cIAP1 autoubiquitination leading to its own degradation, and cIAP1 shuttles between nucleus and cytoplasm via CRM1-dependent export with TRAF2 acting as a cytoplasmic anchor.

    Evidence In vitro ubiquitination with purified RIP1, Smac-stimulated auto-ubiquitination assays, leptomycin B treatment, NES mutagenesis, subcellular fractionation

    PMID:14960576 PMID:15147886 PMID:15265700 PMID:15861135

    Open questions at the time
    • Ubiquitin chain linkage type on RIP1 not yet determined
    • Physiological significance of nuclear localization unclear
  5. 2005 High

    A paradox in caspase inhibition was resolved: cIAP1 BIR2/BIR3 domains bind caspases-7 and -9 but lack critical residues for catalytic inhibition, unlike XIAP; cIAP1's anti-apoptotic function depends primarily on E3 ligase activity rather than direct caspase inhibition. Separately, cIAP1 was shown to ubiquitinate cIAP2 for degradation.

    Evidence Mutagenesis swapping XIAP residues into cIAP1, fluorogenic caspase assays, cIAP1 knockout mice showing elevated cIAP2

    PMID:15798218 PMID:16339151

    Open questions at the time
    • Whether cIAP1 contributes to caspase regulation primarily via ubiquitin-mediated degradation of caspases not yet tested
  6. 2007 High

    cIAP1's role expanded beyond death signaling: it ubiquitinates Mad1 (Myc antagonist) for proteasomal degradation to promote proliferation, and in vivo loss of Birc2 in zebrafish causes caspase-8-dependent vascular regression, demonstrating essential survival functions.

    Evidence In vitro ubiquitination of Mad1, cell proliferation assays; zebrafish Birc2-null forward-genetic screen with epistasis analysis

    PMID:17934460 PMID:18082613

    Open questions at the time
    • Whether Mad1 ubiquitination operates in physiological Myc-driven contexts unclear
    • Mammalian vascular phenotype of cIAP1 loss not yet demonstrated
  7. 2008 High

    A unified model of cIAP1 in TNF signaling was established: cIAP1/2 are recruited to TNFR1 via TRAF2, ubiquitinate RIP1 with K63-linked chains to maintain TAK1 association and NF-κB activation, and their loss (by IAP antagonists or combined genetic deletion) deubiquitinates RIP1, enabling caspase-8 apoptosis. HSP90β was identified as a stabilizing chaperone.

    Evidence In vitro ubiquitination reconstitution, combined knockout/siRNA, co-IP of native TNFR1 complex, HSP90 inhibitor and isoform-specific siRNA

    PMID:18239673 PMID:18570872 PMID:18621737 PMID:18697935

    Open questions at the time
    • K11-linked chain contribution not yet appreciated
    • Role at TNFR2 not fully defined
  8. 2009 High

    cIAP1's innate immune function was established: it ubiquitinates RIP2 downstream of NOD1/NOD2 for NF-κB activation, and separately ubiquitinates caspases-3/7 via distinct binding modes for proteasomal degradation. A UBA domain was identified that binds polyubiquitin chains and facilitates cIAP1 proteasomal targeting.

    Evidence Birc2/Birc3 knockout mice challenged with NOD agonists; in vitro caspase ubiquitination with IBM motif mutagenesis; SPR/ITC/NMR of UBA-ubiquitin interaction

    PMID:18939944 PMID:19258326 PMID:19464198

    Open questions at the time
    • Whether cIAP1 and cIAP2 have non-redundant roles in NOD signaling
    • Structural basis of UBA domain integration with other domains unknown
  9. 2010 High

    Chain-type specificity was refined and necroptosis suppression established: cIAP1 with UbcH5 generates K11-linked chains on RIP1 required for NF-κB; cIAP1 also prevents RIP1/RIP3 necrosome formation and ROS-dependent necrosis. An ATM-TRAF6-cIAP1 cytoplasmic module was identified linking DNA damage to NF-κB.

    Evidence In vitro ubiquitination with linkage-specific antibodies and mass spectrometry; necrostatin-1 rescue and RIP3 knockdown; subcellular fractionation of ATM with co-IP

    PMID:20932475 PMID:21052097 PMID:21113135

    Open questions at the time
    • Relative importance of K11 vs. K63 chains on RIP1 in vivo not resolved
    • Whether ATM-cIAP1 module operates in all cell types unknown
  10. 2011 High

    The structural basis of autoinhibition was solved: crystal structures and biochemistry revealed that BIR domains sequester the RING in a monomeric, inactive conformation; the CARD domain provides an additional layer of inhibition; Smac/antagonist binding releases these constraints to enable RING dimerization and E3 activation. Substrate range was extended to RIP3, RIP4, IKKε, and caspase-1.

    Evidence Crystal structure of cIAP1, NMR of CARD, RING dimerization mutagenesis, in vitro ubiquitination of RIP3/4, inflammasome assays in Birc2/3 KO mice

    PMID:21393245 PMID:21549626 PMID:21931591 PMID:22021857 PMID:22195745

    Open questions at the time
    • Full-length structure of activated (dimeric RING) form not available
    • How CARD inhibition is relieved in vivo not defined
  11. 2013 High

    cIAP1's role in kinase activation was demonstrated: it K63-ubiquitinates IKKε at K30/K401, which is required for IKKε kinase activity and oncogenic transformation. OTUB1 was shown to stabilize cIAP1 by removing K48 chains.

    Evidence In vitro ubiquitination, K-to-R mutagenesis, transformation assays; in vitro DUB assay, zebrafish OTUB1 validation

    PMID:23453969 PMID:23524849

    Open questions at the time
    • Whether IKKε ubiquitination by cIAP1 is relevant in physiological immune contexts
    • Relative contribution of OTUB1 vs. USP19 to cIAP1 stability in different tissues
  12. 2017 Medium

    A non-degradative nuclear function was defined: cIAP1 K63-ubiquitinates E2F1 at K161/164, stabilizing it and enhancing transcription of cell-cycle and pro-apoptotic genes during S phase and DNA damage.

    Evidence In vitro ubiquitination, K-to-R mutagenesis of E2F1, ChIP at CCNE/TP73/APAF1 promoters

    PMID:28542143

    Open questions at the time
    • Independent replication needed
    • Whether E2F1 ubiquitination and the previously reported E2F1 transcriptional co-activation are mechanistically linked is unclear
  13. 2019 High

    In vivo epistasis in adult mice defined the survival hierarchy: combined cIAP1/cIAP2 loss causes lethal caspase-8-dependent apoptosis in intestine and liver, rescued by Casp8/Ripk3 co-deletion; residual inflammation depends on NIK-driven noncanonical NF-κB.

    Evidence Conditional double-knockout mice with genetic epistasis (Casp8, Ripk3, Mlkl, NIK deletion)

    PMID:31141691

    Open questions at the time
    • Tissue-specific contributions of cIAP1 vs. cIAP2 not fully dissected
    • Whether chronic low-level cIAP loss contributes to human inflammatory disease
  14. 2022 High

    The E2 partnership for PROTAC-mediated degradation was elucidated: cIAP1 uses UBE2N to build K63 chains that scaffold branched K48/K63 and K11/K48 chains on neo-substrates, recruiting p97/VCP and the proteasome, revealing how cIAP1 chain-type diversity enables targeted protein degradation.

    Evidence In vitro ubiquitination with defined E2 enzymes, UBE2N-KO cells, mass spectrometry chain-linkage analysis

    PMID:36316570

    Open questions at the time
    • Whether branched-chain mechanism applies to endogenous cIAP1 substrates in physiological signaling
    • Structural basis of branched chain assembly unknown

Open questions

Synthesis pass · forward-looking unresolved questions
  • Key unresolved questions include: the full-length structure of the activated (RING-dimerized) form, how CARD autoinhibition is physiologically relieved, the tissue-specific non-redundant functions of cIAP1 vs. cIAP2, and whether the nuclear transcriptional co-activator function of cIAP1 on E2F1 operates independently of its E3 ligase activity.
  • No structure of full-length activated cIAP1 dimer
  • CARD relief mechanism in vivo unknown
  • Nuclear transcriptional functions lack independent replication

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0140096 catalytic activity, acting on a protein 15 GO:0016874 ligase activity 6 GO:0098772 molecular function regulator activity 4
Localization
GO:0005634 nucleus 3 GO:0005886 plasma membrane 3 GO:0005829 cytosol 2 GO:0005783 endoplasmic reticulum 1 GO:0005794 Golgi apparatus 1
Pathway
R-HSA-162582 Signal Transduction 10 R-HSA-392499 Metabolism of proteins 6 R-HSA-5357801 Programmed Cell Death 6 R-HSA-1640170 Cell Cycle 3 R-HSA-168256 Immune System 3
Partners
BIRC3DIABLOHSP90AB1OTUB1RIPK1RIPK2TRAF2TRAF3
Complex memberships
ATM-TRAF6-cIAP1 moduleTNFR1 signalosome (Complex I)cIAP1-TRAF2-TRAF3 complex

Evidence

Reading pass · 55 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
1998 NF-κB transcriptionally activates cIAP1 (c-IAP1) and cIAP2, TRAF1, and TRAF2 as gene targets; the resulting proteins cooperatively suppress TNF-α-induced caspase-8 activation and apoptosis, explaining the anti-apoptotic mechanism of NF-κB. Reporter assays, gene transfection, dominant-negative NF-κB, apoptosis assays (etoposide and TNF-α stimulation) Science High 9733516
1997 cIAP1 and cIAP2 directly bind caspases-3 and -7 (but not caspase-8, -1, or -6) via their BIR domains and inhibit caspase-3 and -7 activity in vitro (Ki ≤0.1 µM), and suppress cytochrome c-induced caspase activation in cell-free and intact cell systems. In vitro binding (pulldown), in vitro caspase activity assay, cell-free caspase activation system, gene transfection overexpression in cells The EMBO journal High 9384571
2005 cIAP1 BIR2 and BIR3 domains bind caspases-7 and -9 but cannot inhibit caspase activity due to critical substitutions in caspase-inhibitory interaction sites; substituting XIAP residues into cIAP1 BIR domains converts them into tight caspase inhibitors. In vitro binding assays, fluorogenic caspase activity assays, mutagenesis (residue substitution) The Journal of biological chemistry High 16339151
2008 cIAP1 and cIAP2 function as E3 ubiquitin ligases that maintain constitutive K63-linked polyubiquitination of RIP1, keeping it associated with pro-survival TAK1; when cIAPs are degraded by IAP antagonists, deubiquitinated RIP1 binds caspase-8 and induces apoptosis. In vitro ubiquitination assay with purified components, co-immunoprecipitation, siRNA knockdown, IAP antagonist (AEG40730) treatment Molecular cell High 18570872
2008 cIAP1 and cIAP2 are critical and redundant mediators of TNF-α-induced RIP1 polyubiquitination and downstream NF-κB activation; combined genetic/siRNA loss of both cIAPs abrogates RIP1 ubiquitination, impairs IKKβ phosphorylation, and sensitizes cells to TNF-α-induced apoptosis. Combined genetic knockout and siRNA knockdown, co-immunoprecipitation, in vitro ubiquitination reconstitution with purified cIAP1 and UbcH5a The Journal of biological chemistry High 18621737
2008 Both cIAP1 and cIAP2 are recruited to the TNFR1 signalosome along with TRAF2 upon TNF-α treatment; either cIAP1 or cIAP2 is required for RIP1 polyubiquitination and NF-κB signaling, demonstrating functional redundancy. Combined genetic knockout and siRNA knockdown in cultured and primary cells, co-immunoprecipitation, IKKβ phosphorylation assay Proceedings of the National Academy of Sciences of the United States of America High 18697935
2002 c-IAP1 functions as an E3 ubiquitin ligase that ubiquitinates TRAF2 (but not TRAF1 despite binding both), leading to proteasomal degradation of TRAF2 upon TNF-RII engagement; E3-defective c-IAP1 blocked TRAF2 degradation and inhibited apoptosis. In vitro ubiquitination assay, co-immunoprecipitation (pulldown of TRAF1 and TRAF2), RING-domain E3-defective mutant analysis, proteasome inhibitor treatment Nature High 11907583
2010 c-IAP1 and UbcH5 family E2 enzymes collaborate to promote K11-linked polyubiquitination of RIP1 in vitro and in vivo within the TNFR1 signaling complex; endogenous K11-linked ubiquitination of RIP1 is c-IAP1- and UbcH5-dependent and required for TNF-α-stimulated NF-κB activation. Directed yeast two-hybrid for E2 partners, in vitro ubiquitination assay with linkage-specific antibodies, siRNA knockdown, mass spectrometry The EMBO journal High 21113135
2009 cIAP1 and cIAP2 are required for NOD1/NOD2-mediated innate immunity by functioning as E3 ubiquitin ligases that ubiquitinate RIP2, enabling downstream NF-κB and cytokine signaling; Birc2−/− or Birc3−/− macrophages are defective in NOD signaling in vitro and in vivo. Birc2/Birc3 knockout mice, siRNA knockdown, in vitro ubiquitination assay, in vivo NOD agonist challenge, colitis model Immunity High 19464198
2010 Activated ATM translocates to the cytoplasm in a calcium-dependent manner and activates TRAF6 through a TRAF-binding motif; this recruits cIAP1 to an ATM-TRAF6-cIAP1 module that stimulates TAB2-dependent TAK1 phosphorylation and IKKγ monoubiquitination, linking nuclear DNA damage to cytoplasmic NF-κB activation. Subcellular fractionation, co-immunoprecipitation, in vitro ubiquitination assay, calcium chelation, dominant-negative mutants Molecular cell High 20932475
2011 IAP antagonists (Smac mimetics) binding to BIR domains of cIAP1 induce conformational rearrangements that relieve RING domain sequestration within a compact monomeric structure, enabling RING dimerization and E3 ligase activation leading to autoubiquitination and proteasomal degradation. Crystal structure determination, biochemical assays, mutagenesis of RING dimerization interface Science High 22021857
2011 RING dimerization is essential for cIAP1 E3 ligase activity; BIR domains inhibit RING dimerization, causing cIAP1 to exist predominantly as an inactive monomer; Smac mimetics relieve BIR-mediated inhibition, allowing RING dimerization and E3 ligase activation. Mutagenesis of RING dimerization interface, gel-filtration/sedimentation assays, in vitro autoubiquitylation assay The Journal of biological chemistry High 21393245
2011 The CARD domain of cIAP1 autoinhibits its E3 ligase activity by preventing RING dimerization, E2 binding, and E2 activation; structure of the CARD was solved and shown to suppress cell proliferation, migration, and caspase-8-dependent apoptosis and vascular tree degeneration in vivo. NMR structure of CARD domain, RING dimerization assay, mutagenesis, cell proliferation/migration assays, zebrafish in vivo model Molecular cell High 21549626
2004 Upon TNF-R2 stimulation, cIAP1-TRAF2 complex translocates to a perinuclear ER-associated compartment where ER-resident E2 Ubc6 binds cIAP1 and serves as cognate E2 for c-IAP1-mediated TRAF2 ubiquitination and degradation. Confocal microscopy with ER markers, in vitro E2 ubiquitination assay, dominant-negative Ubc6 mutant, Triton X-100 fractionation The EMBO journal High 15861135
2005 c-IAP1 directly ubiquitinates c-IAP2 in an E3-dependent manner (requiring intact RING domain), potentiated by TRAF2 as an adaptor, resulting in proteasomal degradation of c-IAP2; c-IAP1 knockout mice show elevated c-IAP2 protein without increased mRNA. c-IAP1 knockout mouse generation, transfection with wild-type vs. E3-defective c-IAP1, co-immunoprecipitation, Western blot Molecular and cellular biology High 15798218
2004 c-IAP1 and c-IAP2 directly ubiquitinate RIP1 in vitro; RIP1 intermediate and death domains are required for this ubiquitination; cIAP expression decreases steady-state RIP1 levels in a RING- and proteasome-dependent manner. In vitro ubiquitination assay with purified proteins, transfection with RING-domain mutants, proteasome inhibitor treatment FEBS letters High 15147886
2009 cIAP1 binds caspase-3 (via prodomain in a non-classical IBM manner) and caspase-7 (via an exposed AKPD IAP-binding motif on the N-terminus of the large subunit) at distinct processing steps, and ubiquitinates them via UbcH5 subfamily E2 enzymes, promoting their proteasomal degradation in vivo. In vitro binding assays, in vitro caspase activity assay, in vitro ubiquitination assay, mutagenesis (AKPD motif), proteasome inhibitor treatment, site-specific deletion mutants The Journal of biological chemistry High 19258326
2011 cIAP1, cIAP2, and TRAF2 interact with caspase-1-containing complexes and mediate K63-linked polyubiquitination of caspase-1, which is required for efficient inflammasome-dependent caspase-1 activation; Birc2−/− or Birc3−/− mice show impaired caspase-1 activation and resistance to peritonitis. Co-immunoprecipitation, in vitro ubiquitination assay, Birc2/Birc3 knockout mice, inflammasome activation assays, in vivo peritonitis model Immunity High 22195745
2008 Small molecule ME-BS directly interacts with the BIR3 domain of cIAP1 and promotes RING-domain-dependent autoubiquitylation and proteasomal degradation selectively for cIAP1 (not XIAP or cIAP2), sensitizing cancer cells to apoptosis. Direct binding assay (BIR3 interaction), in vitro autoubiquitylation assay, proteasome inhibitor rescue, apoptosis assays The Journal of biological chemistry Medium 18230607
2004 Smac/DIABLO selectively causes rapid degradation of c-IAP1 and c-IAP2 (but not XIAP or Livin) by enhancing their auto-ubiquitination; Smac binding to BIR domains is prerequisite, requiring UbcH5a and UbcH6 E2 enzymes. In vitro ubiquitination assay, pulldown, deletion mutant analysis, transfection The Journal of biological chemistry Medium 14960576
2008 Upon FN14 ligand binding, a cIAP1-TRAF2 complex is recruited to FN14, then undergoes lysosomal (not proteasomal) degradation in a cIAP1-dependent manner, leading to noncanonical NF-κB activation and sensitization of tumor cells to autocrine TNF-α-induced death. Co-immunoprecipitation, lysosomal inhibitor vs. proteasomal inhibitor treatment, cIAP1-TRAF2 overexpression rescue, cell death assays The Journal of cell biology Medium 18606850
2009 OTUB1 deubiquitinase associates with c-IAP1 and disassembles K48-linked polyubiquitin chains from c-IAP1 in vitro and in vivo, stabilizing c-IAP1 and thereby maintaining TWEAK-receptor-mediated canonical NF-κB and MAPK signaling. Co-immunoprecipitation, in vitro deubiquitination assay, siRNA knockdown, zebrafish in vivo validation of c-IAP stability The EMBO journal High 23524849
2011 USP19 deubiquitinase interacts with c-IAP1 and c-IAP2, removes ubiquitin from c-IAPs in vitro, and stabilizes c-IAP levels in vivo; USP19 knockdown enhances TNF-α-induced caspase activation and apoptosis in a c-IAP-dependent manner. Co-immunoprecipitation, in vitro deubiquitination assay, siRNA knockdown, apoptosis assays, overexpression The Journal of biological chemistry Medium 21849505
2013 A cIAP1/cIAP2/TRAF2 E3 ubiquitin ligase complex binds to and ubiquitinates IKKε with K63-linked chains at K30 and K401, which is required for IKKε kinase activity, NF-κB activation, and IKKε-induced malignant transformation. Co-immunoprecipitation, in vitro ubiquitination assay, mutagenesis of ubiquitination sites (K30R/K401R), NF-κB reporter assays, transformation assays Cell reports High 23453969
2007 cIAP1 functions as a ubiquitin E3 ligase that ubiquitinates Mad1 (a Myc antagonist), accelerating its 26S proteasomal degradation; reduction of Mad1 levels cooperates with Myc to promote cell proliferation. In vitro ubiquitination assay, co-immunoprecipitation, proteasome inhibitor rescue, cell proliferation assays Molecular cell High 18082613
2011 cIAP1 and cIAP2 are direct E3 ubiquitin ligases for RIP3 and RIP4 (in addition to RIP1 and RIP2); cIAP1 conjugates diverse ubiquitin chain types including linear chains to all four RIP kinases; cIAP1/2 repression affects NF-κB activation dependent on RIP1–4; K51 and K145 of RIP4 are critical ubiquitination sites. Co-immunoprecipitation (pulldown of RIP1-4), in vitro ubiquitination assay, siRNA knockdown, NF-κB reporter assay, mutagenesis of RIP4 lysines PloS one High 21931591
2000 cIAP1 is cleaved during apoptosis by caspase-3 to generate C-terminal fragments containing the RING domain; the C-terminal spacer-RING fragment suppresses antiapoptotic BIR function and itself induces apoptosis, while the RING domain's E3 ligase activity promotes autoubiquitination and degradation. In vitro caspase-3 cleavage assay, cell transfection with deletion mutants, apoptosis assays, Western blot The Journal of biological chemistry Medium 11106668
2005 cIAP1 localizes predominantly to the nucleus in non-apoptotic cells; apoptotic stimuli induce caspase-dependent nuclear export of cIAP1; during mitosis, cIAP1 redistributes to cytosol then re-accumulates in nuclei in late anaphase/telophase and associates with the midbody; cIAP1 interacts with Survivin during mitosis; cIAP1 overexpression causes G2/M accumulation, cytokinesis defects, and mitotic checkpoint abnormalities. Immunofluorescence microscopy, subcellular fractionation, caspase inhibitor treatment, stable overexpression, co-immunoprecipitation (Survivin interaction), flow cytometry, live cell imaging Cancer research Medium 15665297
2004 cIAP1 and cIAP2 are nuclear-cytoplasmic shuttling proteins; their nuclear export is CRM1-dependent; a leucine-rich NES in the BIR2-BIR3 linker region mediates cIAP1 export; TRAF2 interaction retains cIAP1/cIAP2 in the cytoplasm and prevents nuclear translocation; TNF-α treatment reduces TRAF2-mediated cytoplasmic retention. Leptomycin B treatment, NES mutagenesis, subcellular fractionation, co-immunoprecipitation, co-expression of TRAF2 Experimental cell research Medium 15265700
2004 c-IAP1 translocates from the nucleus to the Golgi apparatus (cytoplasmic side) during monocyte-to-macrophage differentiation via a CRM1/leptomycin B-sensitive nuclear export signal located in the CARD domain. Immunofluorescence microscopy, subcellular fractionation, leptomycin B treatment, site-directed mutagenesis of NES in CARD domain, differentiation assays Blood Medium 15187025
2007 Birc2 (cIAP1) is essential for endothelial cell survival and blood vessel homeostasis in vivo; Birc2 positively regulates formation of the TNFR complex I in endothelial cells to promote NF-κB activation; loss of Birc2 leads to caspase-8-dependent apoptosis and vascular regression. Zebrafish forward-genetic null mutant, genetic epistasis (rescue experiments), molecular pathway analysis of TNFR complex formation, apoptosis assays Nature genetics High 17934460
2008 cIAP1-mediated TRAF2 degradation is required for monocyte-to-macrophage differentiation; cytoplasmic cIAP1 ubiquitinates TRAF2 leading to its proteasomal degradation, which is initially required for early NF-κB/differentiation signaling and subsequently for macrophages to produce proinflammatory cytokines in response to CD40L. siRNA knockdown of cIAP1, TRAF2 overexpression, caspase inhibitor assays, NF-κB nuclear translocation assay, cytokine ELISA Blood Medium 18827186
2009 cIAP1 contains a ubiquitin-associated (UBA) domain between its BIR domains and RING that binds mono-ubiquitin and K48/K63-linked polyubiquitin chains; UBA domain mutations that abrogate ubiquitin binding reduce antagonist-stimulated proteasomal degradation of cIAP1, suggesting the UBA domain facilitates interaction with the proteasome. Surface plasmon resonance (SPR), isothermal titration calorimetry (ITC), NMR mapping of UBA-ubiquitin interaction, UBA domain mutagenesis, proteasomal degradation assays The Biochemical journal High 18939944
2003 HTRA2 serine protease, whose transcription is increased by p53, interacts with cIAP1 and irreversibly cleaves it during p53-dependent apoptosis; serine protease inhibitors block cIAP1 cleavage and inhibit p53-dependent apoptosis. Co-immunoprecipitation (HTRA2-cIAP1 interaction), serine protease inhibitors, p53 transcription assay (HTRA2 induction), apoptosis assays with caspase readouts Genes & development Medium 12569127
2010 cIAP1 protects cells from TNF-induced necrosis by preventing RIP1/RIP3-dependent reactive oxygen species (ROS) production; loss of cIAP1 (via siRNA or IAP antagonist BV6) enhances RIP1 kinase activity, promotes RIP1-RIP3 necrosome formation, and elevates RIP1 kinase-dependent ROS accumulation. siRNA knockdown of individual IAPs, RIP1 kinase inhibitor (necrostatin-1), RIP3 knockdown, ROS measurement, necrosome co-immunoprecipitation Cell death and differentiation Medium 21052097
2012 cIAP1 and cIAP2 limit macrophage necroptosis by inhibiting RIP1 and RIP3 expression via post-transcriptional mechanisms, preventing necrosome formation; loss of cIAP1 specifically sensitizes macrophages to TNF-dependent necroptosis. Smac mimetic treatment, specific knockout mice, RIP1 kinase inhibitor, RIP3 knockdown, cell death assays Cell death and differentiation Medium 22576661
2012 Loss of cIAP1 leads to constitutive activation of the noncanonical NF-κB pathway, increasing myoblast fusion; TWEAK (at low concentrations) activates noncanonical NF-κB to promote myoblast fusion; cIAP1 is an essential component of TWEAK/FN14 downstream signaling regulating myogenesis. cIAP1-null mice, siRNA knockdown of NF-κB mediators (p100, RelB, IKKα, NIK), TWEAK treatment, overexpression of p52/RelB, myotube fusion quantification Science signaling Medium 23074266
2008 The BIR3 domain of cIAP1 binds the N-terminal peptides of both SMAC and caspase-9 in the same shallow groove in a manner analogous to XIAP-BIR3, with comparable affinities (SMAC 85 nM, caspase-9 48 nM), as revealed by crystal structure. X-ray crystallography of cIAP1-BIR3/peptide complexes, surface plasmon resonance binding measurements Acta crystallographica Section D High 19153467
2011 The N-terminal part of cIAP1 directly interacts with the DNA-binding domain of E2F1 transcription factor in the nucleus, dramatically increasing E2F1 transcriptional activity on CCNE and CCNA promoters; cIAP1 is recruited to E2F1 binding sites in a cell cycle- and differentiation-dependent manner; this function is not shared by cIAP2 or XIAP. Co-immunoprecipitation, chromatin immunoprecipitation (ChIP), luciferase reporter assay, siRNA knockdown, deletion mutant mapping of interaction domain The Journal of biological chemistry Medium 21653699
2006 F-box protein Fbxo7 interacts with cIAP1 and promotes its ubiquitination when co-expressed; cIAP1 and Fbxo7 co-localize in cytoplasm, nucleus, and Golgi-like structures, suggesting Fbxo7 may recruit cIAP1 to an SCF ubiquitin ligase complex. Yeast two-hybrid screen, co-immunoprecipitation, co-localization by fluorescence microscopy, ubiquitination assay in cells Biochemical and biophysical research communications Low 16510124
2003 cIAP1, TRAF2, TRAF3, and Smac are endogenously associated with the lymphotoxin-β receptor (LTβR) signaling complex in U937 cells, identified by mass spectrometry of affinity-purified LIGHT·LTβR complex, and confirmed by co-immunoprecipitation. Affinity purification of endogenous receptor complex, mass spectrometry, co-immunoprecipitation The Journal of biological chemistry Medium 12571250
2014 cIAP1 ubiquitinates MEKK2 and MEKK3 with predominantly K63-linked ubiquitin chains, which physically impedes MEK5-ERK5 interaction, leading to ERK5 inactivation; loss of cIAP1 leads to hyperactivation of ERK5. Co-immunoprecipitation, in vitro ubiquitination assay, siRNA knockdown, ERK5 phosphorylation assay, PB1 domain competition assay The EMBO journal Medium 24975362
2014 NIK contains an IAP-binding motif (IBM) at its amino-terminus; NIK IBM interacts with the BIR2 domain of c-IAP1; this interaction enables c-IAP1-mediated ubiquitylation and degradation of NIK, suppressing noncanonical NF-κB signaling basally. IBM mutagenesis, co-immunoprecipitation (BIR domain mapping), in vitro ubiquitination assay, NF-κB target gene expression assays The Journal of biological chemistry Medium 25246529
2015 BIRC2 (cIAP1) functions as a negative regulator of LTR-dependent HIV-1 transcription by repressing the noncanonical NF-κB pathway; Smac mimetic-mediated depletion of BIRC2 reverses HIV-1 latency in a JLat model and synergizes with HDACi panobinostat to activate latent virus in resting CD4+ T cells from ART-suppressed patients. Targeted RNAi screen, siRNA knockdown, Smac mimetic treatment, LTR-reporter assay, latency reversal assay in primary resting CD4+ T cells Cell host & microbe Medium 26355217
2008 HSP90β interacts with c-IAP1 as a client protein in a chaperone relationship; HSP90β inhibition or siRNA depletion leads to c-IAP1 auto-ubiquitination and proteasomal degradation; this interaction is required for c-IAP1 stability and nuclear-to-cytoplasmic transit during differentiation. Co-immunoprecipitation, siRNA depletion of HSP90α vs. HSP90β (isoform specificity), small molecule HSP90 inhibitors, ubiquitination assay, differentiation assays Cell death and differentiation Medium 18239673
2017 cIAP1 mediates K63-linked non-degradative polyubiquitination of E2F1 at lysine residues K161/164, which stabilizes E2F1 and promotes its transcriptional activity and DNA binding to CCNE, TP73, and APAF1 promoters during S phase and in response to DNA damage. In vitro ubiquitination assay, mutagenesis of E2F1 K161/164, ChIP, co-immunoprecipitation, luciferase reporter assay, DNA damage (etoposide) treatment Cell death & disease Medium 28542143
2009 NF45 is an IRES trans-acting factor that enhances cap-independent (IRES-mediated) translation of endogenous cIAP1 mRNA during ER stress/unfolded protein response; NF45 knockdown prevents IRES-mediated cIAP1 protein induction without affecting mRNA levels. RNA affinity chromatography (IRES binding protein identification), enzymatic cleavage mapping of IRES structure, siRNA knockdown of NF45, IRES-luciferase reporter assay, Western blot Cell death and differentiation Medium 19893574
2008 UV irradiation induces hnRNP A1 cytoplasmic accumulation where it binds a 3'UTR AU-rich element of cIAP1 mRNA and enhances its destabilization, reducing cIAP1 levels; hnRNP A1 knockdown restores cIAP1 levels and prevents UV-induced NF-κB activation. mRNA stability assays, 3'UTR reporter constructs, RNA-protein binding assay (identification of hnRNP A1), siRNA knockdown, NF-κB reporter assay Cell death and differentiation Medium 18846111
2022 cIAP1-based PROTAC degraders require the K63-specific E2 enzyme UBE2N; UBE2N promotes cIAP1 ligand-induced K63-linked ubiquitin chains that facilitate assembly of branched K48/K63 and K11/K48 ubiquitin chains on neo-substrates, recruiting p97/VCP, UCH37, and the proteasome for degradation. In vitro ubiquitination assay with specific E2 enzymes, UBE2N knockout cells, mass spectrometry-based ubiquitin chain linkage analysis, proteasome interaction assays Nature chemical biology High 36316570
2012 cIAP1 binds and processes PCSK9 protein; cIAP1 acts as an E3 ubiquitin ligase for PCSK9 via K27-linked ubiquitin chains, promoting lysosomal localization; knockdown of cIAP1 impairs PCSK9 autocatalytic processing, and cIAP1-null MEFs show decreased secreted PCSK9 and increased LDLR. Shotgun proteomics (co-IP/MS), co-immunoprecipitation, in vitro ubiquitination assay with K27-only ubiquitin mutant, cIAP1-null MEFs, Western blot Molecules Low 23085658
2018 cIAP1 is recruited to the TNFR2 signaling complex where it promotes K63-linked polyubiquitination; cIAP1 recruitment is required for subsequent HOIP/LUBAC recruitment and M1-linked polyubiquitination at TNFR2, with both E3 ligases required for TNFR2-induced canonical NF-κB activation. Co-immunoprecipitation (TNFR2 complex pulldown), linkage-specific ubiquitin antibodies, cIAP antagonist treatment, siRNA knockdown, NF-κB reporter assay Biochemical pharmacology Medium 29378181
2019 Combined cIAP1/cIAP2 deficiency in adult mice causes rapid weight loss, inflammation, and caspase-8-dependent cell death predominantly in intestine and liver; genetic deletion of Casp8 and Ripk3 prevents aberrant cell death and prolongs survival; residual inflammation is reduced by NIK inhibition. Conditional and constitutive knockout mice (cIap1/cIap2 double KO), genetic epistasis (Casp8, Ripk3, Mlkl, NIK deletion/inhibition), cleaved caspase-3/8 immunostaining Cell reports High 31141691
2022 TRIM56 interacts with cIAP1 and deubiquitinates it (via TRIM56's zinc finger domain), reducing cIAP1 degradation and increasing its protein levels to promote glioblastoma progression. Co-immunoprecipitation, Human Ubiquitin Array, deletion mutant mapping (zinc finger domain), in vivo xenograft model Journal of experimental & clinical cancer research Low 36471347
2021 OTUB1 reduces K48-linked polyubiquitination of c-IAP1 in hepatocytes, preventing its degradation; OTUB1 deficiency leads to c-IAP1 degradation, reduced K63-linked RIPK1 ubiquitination, RIPK1 phosphorylation, necrosome formation, and lethal hepatocyte necroptosis during bacterial or sterile inflammation. Hepatocyte-specific OTUB1 knockout mice, necrostatin-1s and MLKL deletion rescue, co-immunoprecipitation, K48/K63 ubiquitin linkage analysis, in vitro and in vivo infection models Cell death and differentiation High 33712742
2020 Crystal structures and NMR/biophysical studies of BTK-degrader-cIAP1 ternary complexes reveal that increased ternary complex stability or rigidity does not necessarily correlate with increased degradation efficiency for cIAP1-recruiting PROTACs. X-ray crystallography of ternary complexes, NMR, biophysical binding measurements (SPR/ITC), cellular degradation assays Nature chemical biology High 33199914

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.) 2437 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 926 18570872
2008 c-IAP1 and c-IAP2 are critical mediators of tumor necrosis factor alpha (TNFalpha)-induced NF-kappaB activation. The Journal of biological chemistry 463 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 450 18697935
2002 TNF-RII and c-IAP1 mediate ubiquitination and degradation of TRAF2. Nature 389 11907583
2005 The human anti-apoptotic proteins cIAP1 and cIAP2 bind but do not inhibit caspases. The Journal of biological chemistry 300 16339151
2010 c-IAP1 and UbcH5 promote K11-linked polyubiquitination of RIP1 in TNF signalling. The EMBO journal 296 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 286 19464198
2010 A cytoplasmic ATM-TRAF6-cIAP1 module links nuclear DNA damage signaling to ubiquitin-mediated NF-κB activation. Molecular cell 244 20932475
2002 Synthetic Smac/DIABLO peptides enhance the effects of chemotherapeutic agents by binding XIAP and cIAP1 in situ. The Journal of biological chemistry 229 12218061
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
2011 Antagonists induce a conformational change in cIAP1 that promotes autoubiquitination. Science (New York, N.Y.) 179 22021857
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 166 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 141 22195745
2008 Small molecules destabilize cIAP1 by activating auto-ubiquitylation. The Journal of biological chemistry 136 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
2011 Smac mimetics activate the E3 ligase activity of cIAP1 protein by promoting RING domain dimerization. The Journal of biological chemistry 133 21393245
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 128 22576661
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
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
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 115 28723569
2016 Development of BCR-ABL degradation inducers via the conjugation of an imatinib derivative and a cIAP1 ligand. Bioorganic & medicinal chemistry letters 102 27666635
2013 OTUB1 modulates c-IAP1 stability to regulate signalling pathways. The EMBO journal 101 23524849
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 95 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 Molecular determinants of Smac mimetic induced degradation of cIAP1 and cIAP2. Cell death and differentiation 88 21331077
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
2020 Snapshots and ensembles of BTK and cIAP1 protein degrader ternary complexes. Nature chemical biology 86 33199914
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
2015 Fragment-Based Drug Discovery Targeting Inhibitor of Apoptosis Proteins: Discovery of a Non-Alanine Lead Series with Dual Activity Against cIAP1 and XIAP. Journal of medicinal chemistry 70 26218264
2012 TWEAK and cIAP1 regulate myoblast fusion through the noncanonical NF-κB signaling pathway. Science signaling 70 23074266
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
2007 c-IAP1 cooperates with Myc by acting as a ubiquitin ligase for Mad1. Molecular cell 65 18082613
2013 IKKε-mediated tumorigenesis requires K63-linked polyubiquitination by a cIAP1/cIAP2/TRAF2 E3 ubiquitin ligase complex. Cell reports 61 23453969
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 54 31141691
2016 LCL161 increases paclitaxel-induced apoptosis by degrading cIAP1 and cIAP2 in NSCLC. Journal of experimental & clinical cancer research : CR 54 27737687
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
2008 The RING domain of cIAP1 mediates the degradation of RING-bearing inhibitor of apoptosis proteins by distinct pathways. Molecular biology of the cell 51 18434593
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
2009 NF45 functions as an IRES trans-acting factor that is required for translation of cIAP1 during the unfolded protein response. Cell death and differentiation 47 19893574
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 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
2008 hnRNP A1 regulates UV-induced NF-kappaB signalling through destabilization of cIAP1 mRNA. Cell death and differentiation 44 18846111
2014 Role of the TWEAK-Fn14-cIAP1-NF-κB Signaling Axis in the Regulation of Myogenesis and Muscle Homeostasis. Frontiers in immunology 43 24550918
2008 Designing Smac-mimetics as antagonists of XIAP, cIAP1, and cIAP2. Biochemical and biophysical research communications 43 18992220
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 42 32002309
2003 Akt activity in endometrial cancer cells: regulation of cell survival through cIAP-1. International journal of oncology 41 12888921
2020 BIRC2 Expression Impairs Anti-Cancer Immunity and Immunotherapy Efficacy. Cell reports 40 32846130
2008 cIAP1-dependent TRAF2 degradation regulates the differentiation of monocytes into macrophages and their response to CD40 ligand. Blood 39 18827186
2021 OTUB1 prevents lethal hepatocyte necroptosis through stabilization of c-IAP1 during murine liver inflammation. Cell death and differentiation 38 33712742
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
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
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
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
2022 cIAP1-based degraders induce degradation via branched ubiquitin architectures. Nature chemical biology 32 36316570
2021 Targeting c-IAP1, c-IAP2, and Bcl-2 Eliminates Senescent Glioblastoma Cells Following Temozolomide Treatment. Cancers 32 34298797
2004 An antisense oligonucleotide to cIAP-1 sensitizes prostate cancer cells to fas and TNFalpha mediated apoptosis. The Prostate 32 15065090
2010 Lipopolysaccharide induces autophagy through BIRC2 in human umbilical vein endothelial cells. Journal of cellular physiology 30 20458734
2015 Oncogenic activity of BIRC2 and BIRC3 mutants independent of nuclear factor-κB-activating potential. Cancer science 29 26094954
2022 TRIM56 promotes malignant progression of glioblastoma by stabilizing cIAP1 protein. Journal of experimental & clinical cancer research : CR 28 36471347
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
2009 Enhancement of TRAIL cytotoxicity by AG-490 in human ALL cells is characterized by downregulation of cIAP-1 and cIAP-2 through inhibition of Jak2/Stat3. Cell research 28 19564891
2014 Ubiquitin-dependent regulation of MEKK2/3-MEK5-ERK5 signaling module by XIAP and cIAP1. The EMBO journal 27 24975362
2008 The structure of the BIR3 domain of cIAP1 in complex with the N-terminal peptides of SMAC and caspase-9. Acta crystallographica. Section D, Biological crystallography 27 19153467
2021 Shikonin promotes ubiquitination and degradation of cIAP1/2-mediated apoptosis and necrosis in triple negative breast cancer cells. Chinese medicine 26 33526051
2019 Targeted ablation of the cellular inhibitor of apoptosis 1 (cIAP1) attenuates denervation-induced skeletal muscle atrophy. Skeletal muscle 26 31126323
2015 A novel small-molecule IAP antagonist, AZD5582, draws Mcl-1 down-regulation for induction of apoptosis through targeting of cIAP1 and XIAP in human pancreatic cancer. Oncotarget 26 26314849
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 24 28542143
2014 Nuclear factor-κB-inducing kinase (NIK) contains an amino-terminal inhibitor of apoptosis (IAP)-binding motif (IBM) that potentiates NIK degradation by cellular IAP1 (c-IAP1). The Journal of biological chemistry 24 25246529
2002 The susceptibility to Fas-induced apoptosis in normal enterocytes is regulated on the level of cIAP1 and 2. Biochemical and biophysical research communications 24 11812006
2012 c-IAP1 binds and processes PCSK9 protein: linking the c-IAP1 in a TNF-α pathway to PCSK9-mediated LDLR degradation pathway. Molecules (Basel, Switzerland) 23 23085658
2012 Foxa2 may modulate hepatic apoptosis through the cIAP1 pathway. Cellular signalling 23 23275033
2003 15-deoxy-delta 12,14-prostaglandin J2 and laminar fluid shear stress stabilize c-IAP1 in vascular endothelial cells. American journal of physiology. Heart and circulatory physiology 23 12623786