Affinage

BIRC5

Baculoviral IAP repeat-containing protein 5 · UniProt O15392

Round 2 corrected
Length
142 aa
Mass
16.4 kDa
Annotated
2026-04-28
130 papers in source corpus 39 papers cited in narrative 39 extracted findings

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

Survivin (BIRC5) is a bifunctional inhibitor-of-apoptosis (IAP) family protein that serves as an essential subunit of the chromosomal passenger complex (CPC) and a key suppressor of caspase-dependent cell death. As a CPC component alongside Aurora B, INCENP, and Borealin, survivin reads Haspin-deposited histone H3-pThr3 to target the complex to inner centromeres, where it ensures amphitelic kinetochore–spindle attachment, proper chromosome segregation, and cytokinesis completion; it additionally modulates centrosomal microtubule nucleation and dynamics independently of Aurora B (PMID:20929775, PMID:16407408, PMID:15249581). Survivin suppresses apoptosis through multiple routes: direct inhibition of effector caspases-3 and -7, formation of a survivin–HBXIP complex that sequesters pro-caspase-9 from Apaf-1, stabilization of XIAP against proteasomal degradation, and release of a mitochondrial survivin pool into the cytosol upon apoptotic stimuli (PMID:9850056, PMID:12773388, PMID:15218035, PMID:15489959). Its stability and activity are regulated by CDK1–cyclin B1 phosphorylation at Thr34, Hsp90 chaperoning, CBP-mediated acetylation at Lys129 controlling nuclear export and STAT3 transrepression, Lys63-linked ubiquitination governing centromeric residence, and transcriptional inputs from STAT3, p53, FOXO3, and mTOR/p70S6K1 signaling (PMID:11069302, PMID:14614132, PMID:20826784, PMID:16322459, PMID:12393476).

Mechanistic history

Synthesis pass · year-by-year structured walk · 13 steps
  1. 1997 High

    Identification of survivin as a structurally atypical IAP (single BIR, no RING) that is cancer-restricted in adults and sufficient to block apoptosis established a new node linking cell-death control to oncogenesis.

    Evidence cDNA cloning, Northern blot across tissues and tumors, IL-3-withdrawal apoptosis rescue in B-cell precursors

    PMID:9256286

    Open questions at the time
    • Mechanism of apoptosis inhibition unknown
    • Endogenous interactors unidentified
    • Role in normal cell biology undefined
  2. 1998 High

    Demonstrating that survivin is cell-cycle-restricted to G2/M, associates with mitotic spindle microtubules, and directly binds and inhibits effector caspases-3 and -7 linked its anti-apoptotic function to mitosis and established a molecular target specificity.

    Evidence Cell-cycle synchronization with microtubule co-sedimentation; in vitro caspase binding and inhibition assays; antisense knockdown showing requirement for cell viability

    PMID:9556606 PMID:9850056 PMID:9859993

    Open questions at the time
    • Whether direct caspase binding is the primary physiological mechanism was debated
    • How survivin reaches microtubules mechanistically unclear
    • No structural information on the BIR–caspase interface
  3. 2000 High

    Discovery that CDK1–cyclin B1 phosphorylates survivin at Thr34 to maintain a survivin–caspase-9 complex, and that survivin behaves as a chromosomal passenger protein with characteristic relocalization from kinetochores to midbody, unified its mitotic and anti-apoptotic roles under cell-cycle kinase control.

    Evidence In vitro kinase assay, T34A mutagenesis with caspase-9 dissociation readout; HA-tagged survivin immunofluorescence with mutational dissection; survivin-null mouse embryos showing disrupted microtubule formation and embryonic lethality

    PMID:11069302 PMID:11084331 PMID:11134084

    Open questions at the time
    • Which apoptosis pathway (intrinsic vs extrinsic) is the primary physiological target remained open
    • How survivin is recruited to kinetochores unknown
    • Whether the passenger phenotype and the caspase-inhibition phenotype are separable
  4. 2003 High

    Identification of the survivin–HBXIP complex as a selective inhibitor of caspase-9 recruitment to Apaf-1, and of survivin–Smac/DIABLO interaction as a mechanism to relieve Smac inhibition of XIAP, revealed that survivin's anti-apoptotic function operates largely through modulating other IAP and apoptosome components rather than solely through direct caspase binding.

    Evidence In vitro reconstitution of survivin–HBXIP–procaspase-9 complex with cell-free apoptosis assay; GST pulldown and mutagenesis (D71R) of survivin–Smac interaction; Hsp90–survivin co-IP with domain mapping showing BIR-dependent chaperoning

    PMID:12660240 PMID:12773388 PMID:14614132

    Open questions at the time
    • Relative contribution of direct caspase inhibition vs indirect mechanisms in vivo unresolved
    • Structural basis of survivin–HBXIP–caspase-9 ternary complex unknown
    • How the mitochondrial pool of survivin is separately regulated was not yet defined
  5. 2004 High

    Identification of Borealin as the fourth CPC subunit and demonstration that the intact CPC is required for chromatin-induced microtubule stabilization (opposing MCAK) in Xenopus extracts established the holocomplex architecture and a key mitotic function; concurrently, discovery of a mitochondrial survivin pool discharged upon apoptotic stimuli defined a spatially distinct anti-apoptotic mechanism.

    Evidence TAP purification of Aurora B complex identifying Borealin; Xenopus egg extract depletion/MCAK co-depletion rescue; subcellular fractionation plus mitochondria-targeted survivin constructs with xenograft validation

    PMID:15249581 PMID:15260989 PMID:15489959

    Open questions at the time
    • How survivin is imported into mitochondria mechanistically undefined
    • Whether Borealin–survivin interaction is direct and which surfaces mediate it needed structural resolution
    • Functional redundancy among CPC targeting mechanisms untested
  6. 2005 High

    Revealing that Lys63-linked ubiquitination (by Ufd1) promotes survivin's centromeric association while deubiquitination (by hFAM) drives its dissociation established a non-degradative ubiquitin code governing CPC dynamics at centromeres.

    Evidence Co-IP and ubiquitination assays distinguishing K48 vs K63 chains; RNAi of hFAM/Ufd1 with chromosome segregation analysis

    PMID:16322459

    Open questions at the time
    • Precise ubiquitination sites on survivin not mapped
    • How K63-Ub promotes centromere binding mechanistically unclear
    • Whether other DUBs regulate survivin's centromeric pool
  7. 2006 High

    Quantitative live-imaging showed survivin modulates centrosomal microtubule nucleation rates and catastrophe frequency independently of Aurora B kinase activity, establishing a CPC-independent mitotic function.

    Evidence GFP-α-tubulin and GFP-EB1 time-lapse imaging after siRNA depletion of survivin vs pharmacological Aurora B inhibition

    PMID:16407408

    Open questions at the time
    • Molecular mechanism by which survivin suppresses microtubule nucleation unknown
    • Whether this function involves a distinct survivin complex is unresolved
    • Contribution to normal vs cancer cell mitosis not distinguished
  8. 2008 High

    Conditional knockout in DT40 cells definitively separated survivin's essential mitotic function from its anti-apoptotic role: survivin-null cells die from failed cytokinesis, not apoptosis, and CDK phosphorylation sites and Smac/Aurora B-binding residues are dispensable for viability.

    Evidence Conditional KO complemented by structure-function mutants expressed from the null background; etoposide sensitivity unaffected

    PMID:18936249

    Open questions at the time
    • Whether these findings extrapolate to mammalian somatic cells untested
    • Which minimal structural determinants of survivin suffice for CPC function not fully defined
    • Anti-apoptotic function not probed with physiological death stimuli
  9. 2010 High

    Demonstration that survivin directly reads Haspin-deposited H3-pThr3 marks at centromeric nucleosomes, cooperating with Bub1-deposited H2A-pSer121/shugoshin, defined the histone-code-based mechanism targeting the CPC to the inner centromere; concurrently, CBP acetylation at Lys129 was shown to toggle survivin between a nuclear STAT3-repressor form and a CRM1-exported cytoplasmic form.

    Evidence Nucleosome binding assays with phospho-H3 peptides, fission yeast and human cell genetics; site-directed mutagenesis of K129, co-IP with STAT3, luciferase reporter assays

    PMID:20826784 PMID:20929775

    Open questions at the time
    • Structural basis of BIR domain recognition of H3-pT3 not resolved at atomic level
    • Physiological signals controlling CBP acetylation of survivin undefined
    • Integration of acetylation with ubiquitin code at centromeres unexplored
  10. 2012 High

    Discovery that survivin recruits Drp1 to drive mitochondrial fragmentation and inhibits complex I to shift metabolism toward glycolysis, and that in erythroblasts survivin forms a non-canonical complex with Eps15/clathrin to promote enucleation, expanded survivin's functional repertoire well beyond apoptosis and the canonical CPC.

    Evidence Drp1 co-IP and fractionation with oxygen consumption/ROS measurements; proteomics-identified Eps15–clathrin complex in MEL cells, conditional KO erythroblasts rescued by vacuolin-1

    PMID:22491741 PMID:23146905

    Open questions at the time
    • How survivin is directed to mitochondrial complex I not defined
    • Whether the Eps15/clathrin complex exists outside erythropoiesis unknown
    • Physiological significance of survivin-induced glycolytic switch in normal tissues untested
  11. 2014 High

    Survivin depletion was shown to produce merotelic kinetochore attachments, γH2AX foci, and chromosomal aberrations repaired by NHEJ irrespective of p53 status, establishing survivin as a guardian of chromosomal stability through proper amphitelic attachment.

    Evidence RNAi in isogenic p53-null and wild-type lines, spectral karyotyping, ATM/DNA-PK inhibitor epistasis

    PMID:24886358

    Open questions at the time
    • Whether survivin directly senses or corrects merotelic attachments or only ensures CPC function is unclear
    • Long-term genomic consequences of transient survivin loss not characterized
  12. 2021 Medium

    Identification of Hsp60 as an arsenic trioxide target whose disruption degrades survivin, and of a mutant p53–YAP axis driving BIRC5 transcription in esophageal SCC metastasis, added new regulatory inputs controlling survivin abundance in disease contexts.

    Evidence Metalloproteomics with arsenic probe identifying Hsp60; carcinogen-induced ESCC mouse model with shRNA depletion of survivin reducing lung metastasis

    PMID:33737385 PMID:34476069

    Open questions at the time
    • Whether Hsp60 chaperoning is distinct from or redundant with Hsp90 chaperoning unknown
    • Mutant p53–YAP–survivin axis confirmed in one tumor type only
    • Therapeutic exploitability of these axes not validated
  13. 2024 Medium

    TRAF4 was shown to stabilize phospho-survivin via the Akt/Wee1/CDK1 axis by preventing FBXL7-mediated ubiquitination and proteasomal degradation, linking survivin stability to radioresistance in nasopharyngeal carcinoma.

    Evidence TRAF4 knockdown, Akt/Wee1/CDK1 inhibitors, FBXL7 ubiquitination assay, xenograft radiosensitivity model

    PMID:38164179

    Open questions at the time
    • FBXL7 as a survivin E3 ligase confirmed only in NPC cells
    • Specific ubiquitination sites targeted by FBXL7 not mapped
    • Generalizability of TRAF4–survivin axis to other cancers untested

Open questions

Synthesis pass · forward-looking unresolved questions
  • Key unresolved questions include the atomic-resolution structural basis for survivin's recognition of H3-pThr3 nucleosomes, the precise mechanism by which survivin modulates microtubule dynamics independently of Aurora B, the relative quantitative contribution of each anti-apoptotic mechanism in physiological contexts, and whether the non-canonical survivin–Eps15/clathrin and survivin–Drp1 complexes operate broadly or only in specific cell lineages.
  • No high-resolution structure of full-length survivin on a nucleosome
  • Aurora B-independent microtubule regulation mechanism molecularly undefined
  • Quantitative in vivo dissection of individual anti-apoptotic routes lacking

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0098772 molecular function regulator activity 5 GO:0008092 cytoskeletal protein binding 2 GO:0042393 histone binding 1 GO:0140110 transcription regulator activity 1
Localization
GO:0005694 chromosome 4 GO:0005739 mitochondrion 2 GO:0005856 cytoskeleton 2 GO:0005634 nucleus 1 GO:0005829 cytosol 1
Pathway
R-HSA-1640170 Cell Cycle 11 R-HSA-5357801 Programmed Cell Death 11 R-HSA-162582 Signal Transduction 4 R-HSA-392499 Metabolism of proteins 3
Partners
AURKBCDCA8DIABLODRP1HSP90AA1INCENPLAMTOR5XIAP
Complex memberships
Chromosomal passenger complex (CPC)Survivin–Eps15–clathrin complexSurvivin–HBXIP–procaspase-9 complexSurvivin–XIAP complex

Evidence

Reading pass · 39 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
1997 Survivin (BIRC5) was identified as a novel IAP family member containing a single BIR domain and lacking a C-terminal RING finger. It is expressed during fetal development and in human cancers but undetectable in terminally differentiated adult tissues. Recombinant survivin counteracts apoptosis of IL-3-deprived B lymphocyte precursors. cDNA cloning, Northern blot, recombinant expression, apoptosis assay Nature medicine High 9256286
1998 Survivin is expressed in the G2/M phase of the cell cycle and associates with microtubules of the mitotic spindle in a specific and saturable reaction regulated by microtubule dynamics. Disruption of survivin-microtubule interactions results in loss of anti-apoptotic function and increased caspase-3 activity during mitosis. Cell cycle synchronization, co-sedimentation with microtubules, caspase-3 activity assay, immunofluorescence Nature High 9859993
1998 Survivin binds specifically to effector caspases-3 and -7 in vitro and inhibits their activity, protecting cells from apoptosis induced by Fas, Bax, caspases, and anticancer drugs. It does not bind the initiator caspase-8. In vitro binding assay, co-transfection apoptosis assay, cell-free caspase activity assay, gene transfection Cancer research High 9850056
1998 Antisense-mediated knockdown of survivin (via EPR-1 antisense) in HeLa cells suppresses endogenous survivin expression, increases apoptosis, and inhibits cell proliferation, establishing survivin as required for cell viability. Stable transfection with inducible antisense construct, flow cytometry, in situ TUNEL, cell proliferation assay The Journal of biological chemistry High 9556606
1999 Two splice variants of survivin were identified: survivin-ΔEx3 (lacking exon 3) retains anti-apoptotic properties, whereas survivin-2B (retaining part of intron 2) has markedly reduced anti-apoptotic potential, suggesting a regulatory balance between isoforms. RT-PCR, Northern blot, transfection apoptosis assay Cancer research High 10626797
2000 Survivin physically associates with the cyclin-dependent kinase p34(cdc2) on the mitotic apparatus and is phosphorylated on Thr34 by p34(cdc2)-cyclin B1 in vitro and in vivo. Loss of Thr34 phosphorylation results in dissociation of a survivin-caspase-9 complex and caspase-9-dependent apoptosis during mitosis. Co-immunoprecipitation, in vitro kinase assay, phosphorylation-defective mutant (T34A), caspase-9 activity assay Proceedings of the National Academy of Sciences of the United States of America High 11069302
2000 Human survivin localizes as a chromosomal passenger protein: it associates with kinetochores at early mitosis, translocates to the spindle midzone during anaphase, and to the midbody during cleavage. Point mutation C84A or C-terminal deletion (Δ106) disrupts kinetochore/midbody localization. Survivin localization is independent of microtubules. HA-tagged survivin transfection, immunofluorescence, nocodazole/taxol treatment, deletion/point mutants The Journal of cell biology High 11134084
2000 Survivin is required for mitosis during mammalian development: null mouse embryos show disrupted microtubule formation, polyploidy, and fail to survive beyond 4.5 days post coitum. Survivin's cell-cycle localization and knockout phenotype closely parallel those of INCENP, suggesting they act together in the chromosomal passenger complex. Gene knockout (homologous recombination), immunofluorescence, flow cytometry, cell-cycle analysis Current biology : CB High 11084331
2001 Recombinant human survivin expressed as a homodimer binds caspase-3 and caspase-7 with dissociation constants of ~21 nM and ~12 nM respectively (surface plasmon resonance) and potently inhibits their cleavage of PARP and a tetrapeptide substrate in vitro. Survivin co-localizes with caspase-3 on microtubules at centrosomes. Recombinant protein expression, surface plasmon resonance, in vitro caspase activity assay, immunofluorescence Biochemistry High 11170436
2001 A nonphosphorylatable Thr34→Ala survivin mutant delivered by adenovirus causes spontaneous apoptosis in multiple cancer cell lines (but not normal cells) via cytochrome c release, caspase-9 cleavage, and caspase-3 activation, suppressing tumor growth in xenograft models. Adenoviral delivery of dominant-negative T34A mutant, cytochrome c release assay, caspase-9/-3 cleavage assay, xenograft tumor model The Journal of clinical investigation High 11581299
2002 Inhibition of STAT3 signaling in primary effusion lymphoma cells induces transcriptional repression of survivin, leading to caspase-dependent apoptosis. Forced survivin overexpression rescues cells from STAT3 inhibition-induced apoptosis, placing survivin downstream of constitutive STAT3 signaling. Dominant-negative STAT3 transduction, pharmacological STAT3 inhibition, survivin overexpression rescue, caspase activity assay Blood High 12393476
2002 Serum and PDGF-AB stimulate survivin expression in smooth muscle cells, suppressing apoptosis and caspase activation. Adenoviral delivery of the T34A survivin mutant reverses this cytoprotective effect and suppresses neointimal formation after vascular injury in mice. Primary SMC culture, adenoviral gene delivery, caspase activity assay, wire-injury mouse model, in vivo apoptosis assay Nature medicine High 12172543
2003 Survivin directly interacts with Smac/DIABLO both in vitro and in vivo via its BIR motif. A point mutation (D71R) or C-terminal deletion abrogates Smac binding and anti-apoptotic activity. Survivin requires co-presence of Smac/DIABLO and XIAP to inhibit caspase cleavage in a cell-free system; survivin itself does not directly bind caspases in this context. Co-immunoprecipitation, GST pulldown, site-directed mutagenesis, cell-free caspase assay, immunofluorescence co-localization The Journal of biological chemistry High 12660240
2003 Survivin forms a complex with HBXIP (hepatitis B X-interacting protein). The survivin-HBXIP complex, but neither protein alone, binds pro-caspase-9 and prevents its recruitment to Apaf-1, selectively suppressing mitochondria/cytochrome c-initiated apoptosis. Viral HBX also joins this complex to suppress caspase activation in a survivin-dependent manner. Co-immunoprecipitation, GST pulldown reconstitution, caspase-9 recruitment assay, cell-free apoptosis assay The EMBO journal High 12773388
2003 Hsp90 associates with survivin via its ATPase domain interacting with the survivin BIR domain. Disruption of the survivin-Hsp90 complex by pharmacological Hsp90 inhibition or antibody-mediated disruption causes proteasomal degradation of survivin, mitochondrial apoptosis, and mitotic defects. Co-immunoprecipitation, domain-mapping, pharmacological Hsp90 inhibition, proteasome inhibitor rescue, cell cycle and apoptosis analysis Proceedings of the National Academy of Sciences of the United States of America High 14614132
2003 Aurora B kinase activity and formation of the Aurora B/INCENP/survivin complex are both required for proper centromere localization of the complex. Survivin depletion by RNAi phenocopies Aurora B or INCENP depletion. Under identical conditions, survivin does not detectably stimulate Aurora B kinase activity in vitro, while INCENP C-terminal region is sufficient for kinase activation through phosphorylation of INCENP Thr893/Ser894/Ser895. RNAi depletion, dominant-negative Aurora B overexpression, recombinant protein kinase assay, mass spectrometry phosphosite identification, site-directed mutagenesis Molecular biology of the cell High 12925766
2004 Survivin associates with XIAP via conserved BIR domains. The survivin-XIAP complex promotes increased XIAP stability against ubiquitination/proteasomal destruction and synergistic inhibition of apoptosis; this synergy is abolished in XIAP-null cells. Co-immunoprecipitation, ubiquitination assay, XIAP-/- cell complementation, apoptosis assays The Journal of biological chemistry High 15218035
2004 Borealin is identified as a novel component of the chromosomal passenger complex (CPC) alongside Aurora B, INCENP, and survivin. Approximately half of Aurora B co-complexes with all four components; Borealin binds survivin and INCENP in vitro. Borealin depletion causes kinetochore-spindle misattachments and multipolar spindles, implicating the CPC holocomplex in spindle integrity. Tandem-affinity purification, co-immunoprecipitation, in vitro binding, RNAi depletion, immunofluorescence The Journal of cell biology High 15249581
2004 The chromosomal passenger complex (containing Incenp, survivin, Dasra A/B, and Aurora B kinase) is required for chromatin-induced microtubule stabilization and spindle assembly in Xenopus egg extracts. Depletion of the CPC fails microtubule stabilization, which is rescued by co-depletion of MCAK, whose depolymerizing activity is negatively regulated by Aurora B. Xenopus egg extract depletion, microtubule assembly assay, co-immunoprecipitation, immunofluorescence Cell High 15260989
2004 Survivin exists in a novel mitochondrial pool in tumor cells. In response to apoptotic stimulation, mitochondrial survivin is discharged into the cytosol to prevent caspase activation. Selective mitochondrial targeting of survivin enhances soft-agar colony formation and accelerates tumor growth in vivo. Subcellular fractionation, mitochondria-targeted survivin construct, soft-agar assay, xenograft tumor model The Journal of clinical investigation High 15489959
2004 By live-cell FRAP, Survivin-GFP is highly mobile at centromeric chromatin during prometaphase and metaphase (unlike Aurora B-GFP which is relatively immobile). At telophase, both are fully immobile. Survivin's weak centromeric association depends on Aurora B presence, but is unaffected by microtubule-disrupting drugs. FRAP (fluorescence recovery after photobleaching), GFP chimera live imaging, siRNA depletion of Aurora B Cell cycle (Georgetown, Tex.) High 15483398
2005 Ubiquitin regulates survivin's dynamic association with centromeres: Lys63-linked ubiquitination (mediated by Ufd1) is required for survivin's association with centromeres, while Lys63-deubiquitination by hFAM is required for its dissociation. Both Lys48- and Lys63-linked ubiquitin chains are present on survivin in mitosis. This ubiquitin regulation controls chromosome alignment and segregation independently of protein degradation. Co-immunoprecipitation, ubiquitination assay, RNAi depletion of hFAM/Ufd1, immunofluorescence, chromosome segregation analysis Science (New York, N.Y.) High 16322459
2006 siRNA depletion of survivin increases centrosomal microtubule nucleation and microtubule catastrophe frequency, while survivin overexpression reduces nucleation and suppresses microtubule dynamics in mitotic spindles and midbodies. Aurora B depletion/inhibition does not affect these microtubule parameters, indicating survivin modulates microtubule nucleation and dynamics independently of Aurora B. Time-lapse imaging of GFP-α-tubulin and GFP-EB1, siRNA depletion, Aurora B pharmacological inhibition, quantitative microtubule dynamics analysis Molecular biology of the cell High 16407408
2006 IGF-1 increases survivin expression in prostate cancer cells via mTOR-dependent mRNA translation (not transcription or protein stability). The mTOR target p70S6K1 overexpression reproduces this effect; p70S6K1 siRNA knockdown reduces survivin. Rapamycin (mTOR inhibitor) abolishes the IGF-1-induced survivin increase. Western blot, RT-PCR, metabolic pulse-chase (protein stability), rapamycin treatment, p70S6K1 overexpression and siRNA Oncogene High 17072337
2008 Conditional knockout of survivin in chicken DT40 cells results in death in interphase after failure to complete cytokinesis (not apoptosis). Cells lacking survivin show normal sensitivity to etoposide. Mutations in the nuclear export sequence or dimerization interface render cells temperature-sensitive; widely studied CDK phosphorylation sites and Smac/Aurora B binding sites are not essential for viability when survivin is the sole copy expressed. Conditional gene knockout, complementation with survivin mutants against null background, flow cytometry, live-cell imaging The Journal of cell biology High 18936249
2009 DNA methylation of the survivin promoter inhibits p53 binding and prevents p53-mediated transcriptional repression of survivin. Demethylation by decitabine restores p53-dependent survivin repression in endometrial cancer cells. Methylation-specific PCR, pyrosequencing, decitabine treatment, ChIP for p53 binding, reporter assay Oncogene High 19363521
2009 FOXO3/FKHRL1 activation in neuroblastoma cells represses BIRC5/survivin transcription and protein expression. Conditional FKHRL1 activation prevents accumulation of Bim and Bax at mitochondria and cytochrome c release; transgenic survivin overexpression rescues these apoptotic events. Survivin knockdown accelerates FKHRL1-induced apoptosis. Conditional 4-OHT-regulated FKHRL1(A3)ERtm allele, retroviral shRNA knockdown, transgenic survivin overexpression, mitochondrial membrane potential assay, cytochrome c release Molecular biology of the cell High 19211844
2010 CBP-dependent acetylation of survivin on Lys129 promotes its homodimerization and nuclear accumulation. Deacetylation promotes survivin monomer formation, heterodimerization with CRM1, and nuclear export. Nuclear acetylated survivin binds the N-terminal transcriptional activation domain of STAT3 dimers and represses STAT3 transactivation of target gene promoters. Site-directed mutagenesis, co-immunoprecipitation, proteomic analysis, luciferase reporter assay, nuclear fractionation, SNP analysis in neuroblastoma The Journal of biological chemistry High 20826784
2010 PI3K/Akt/p70S6K1 pathway regulates survivin mRNA expression: active PI3K or Akt-induced p70S6K1 activation is sufficient to induce survivin mRNA; PTEN overexpression decreases survivin; rapamycin reduces survivin mRNA levels. Forced expression of active PI3K (v-P3k), wild-type and mutant PTEN, p70S6K1 overexpression, rapamycin treatment, siRNA, RT-PCR Biochemical and biophysical research communications Medium 20361940
2010 Two histone marks cooperate to target the chromosomal passenger complex (CPC) to the inner centromere: H3-Thr3 phosphorylation by Haspin promotes nucleosome binding of survivin, while Bub1-mediated H2A-Ser121 phosphorylation facilitates shugoshin binding of the CPC. Survivin directly reads H3-pT3 to position the CPC at the inner centromere. Fission yeast and human cell genetics, phospho-specific antibodies, ChIP, nucleosome binding assay, kinase assays Science (New York, N.Y.) High 20929775
2011 BIRC5 knockdown in neuroblastoma cells causes multinucleation indicating mitotic catastrophe, which activates p53 and leads to apoptosis via CASP2. CASP2 inhibition rescues the apoptosis, demonstrating that BIRC5 function in the chromosomal passenger complex is essential for microtubule-kinetochore stability in neuroblastoma. Antisense/shRNA knockdown, immunofluorescence (multinucleation), FACS (apoptosis), PARP cleavage, CASP2 inhibitor rescue, p53 activation assay Endocrine-related cancer High 21859926
2012 Survivin induces mitochondrial fragmentation by recruiting the fission regulator Drp1 to mitochondria, inhibits respiratory complex-I (preventing ROS accumulation and FOXO3-induced apoptosis), and represses BCL2L11/Bim. Loss of oxidative phosphorylation is compensated by increased glycolysis; glycolysis inhibitors neutralize survivin's anti-apoptotic effect. Mitochondrial morphology imaging, Drp1 fractionation/co-immunoprecipitation, oxygen consumption assay, ROS measurement, glycolysis inhibitor treatment, apoptosis assays Oncogene High 23146905
2012 In enucleating erythroblasts, survivin forms a novel multi-protein complex with EGF receptor substrate 15 (Eps15) and clathrin (endocytic vesicle trafficking proteins) rather than its canonical CPC partners Aurora B and INCENP. Knockdown of survivin, Eps15, or clathrin reduces enucleation efficiency; loss of survivin in murine erythroblasts inhibits enucleation and reduces cytoplasmic vacuoles; vacuolin-1 (vacuole fusion inducer) rescues survivin-deficient enucleation. Proteomic analysis (survivin pulldown from MEL cells), co-immunoprecipitation, immunofluorescence, conditional survivin-fl/fl knockout, vacuolin-1 rescue experiment Haematologica High 22491741
2013 Merkel cell polyomavirus large T antigen upregulates survivin expression via an intact Rb-targeting domain that activates survivin gene transcription (and E2F1/cyclin E). Survivin expression is critical for MCV-positive MCC cell survival. Transcriptome sequencing, shRNA knockdown of MCV large T antigen, exogenous MCV large T antigen expression, Rb-domain mutant analysis, RT-PCR and Western blot Science translational medicine High 22572880
2013 HER2 stabilizes survivin protein through the HER2/ERK pathway reducing XAF1, thereby diminishing the XIAP-XAF1 E3 ligase complex that ubiquitinates survivin. Simultaneously, HER2/Akt/CDK1-cyclin B1 phosphorylates Thr34 of survivin, stabilizing it. HER2 also suppresses Notch cleavage via γ-secretase inhibition, paradoxically downregulating Notch-dependent survivin transcription. Western blot, co-immunoprecipitation, pharmacological inhibitors of γ-secretase and ERK, shRNA knockdown, ubiquitination assay The Biochemical journal Medium 23323858
2014 Survivin knockdown causes polyploidization in multiple cell lines irrespective of p53 status, and produces merotelic kinetochore-spindle assemblies, γH2AX foci, and DNA damage response. Chromosomal aberrations indicative of non-homologous end joining (NHEJ) repair occur only in survivin-depleted cells, demonstrating survivin safeguards chromosomal stability via proper amphitelic kinetochore-spindle assembly. RNAi knockdown, isogenic p53-null cell lines, flow cytometry, spectral karyotyping, immunofluorescence, ATM/DNA-PK inhibitors Molecular cancer High 24886358
2021 Arsenic trioxide binds to Hsp60 (identified by metalloproteomics), abolishing Hsp60 refolding capability. This disrupts Hsp60-survivin complexes, resulting in survivin degradation in APL cells. Metalloproteomics with organoarsenic probe, quantitative proteomics, biophysical binding assays, cell-based validation of complex disruption Chemical science Medium 34476069
2021 Mutant p53 (Trp53R172H) binds with YAP in esophageal squamous cell carcinoma cells to induce Survivin (BIRC5) expression, promoting lung metastasis. Depletion of Survivin specifically reduces mutant p53-driven lung metastasis, and YAP-BIRC5 was identified as a key axis mediating this effect. Carcinogen-induced mouse ESCC model, shRNA depletion, tail-vein metastasis model, RNA-seq, co-immunoprecipitation of mutant p53 and YAP Genes & development Medium 33737385
2024 TRAF4 overexpression in nasopharyngeal carcinoma promotes radioresistance by activating the Akt/Wee1/CDK1 axis, which phosphorylates survivin and prevents its FBXL7-mediated proteasomal degradation. TRAF4 knockdown decreases phospho-survivin, promotes survivin degradation by FBXL7, and increases radiosensitivity. TRAF4 knockdown, Akt/Wee1/CDK1 pathway inhibitors, FBXL7 ubiquitination assay, xenograft radiosensitivity model, co-expression analysis in NPC tissues International journal of biological sciences Medium 38164179

Source papers

Stage 0 corpus · 130 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
1997 A novel anti-apoptosis gene, survivin, expressed in cancer and lymphoma. Nature medicine 2720 9256286
1998 Control of apoptosis and mitotic spindle checkpoint by survivin. Nature 1619 9859993
2002 Generation and initial analysis of more than 15,000 full-length human and mouse cDNA sequences. Proceedings of the National Academy of Sciences of the United States of America 1479 12477932
2015 The BioPlex Network: A Systematic Exploration of the Human Interactome. Cell 1118 26186194
1998 IAP-family protein survivin inhibits caspase activity and apoptosis induced by Fas (CD95), Bax, caspases, and anticancer drugs. Cancer research 1099 9850056
2017 Architecture of the human interactome defines protein communities and disease networks. Nature 1085 28514442
2020 A reference map of the human binary protein interactome. Nature 849 32296183
2000 DNA cloning using in vitro site-specific recombination. Genome research 815 11076863
2007 Large-scale mapping of human protein-protein interactions by mass spectrometry. Molecular systems biology 733 17353931
2021 Dual proteome-scale networks reveal cell-specific remodeling of the human interactome. Cell 705 33961781
2011 Phylogenetic-based propagation of functional annotations within the Gene Ontology consortium. Briefings in bioinformatics 656 21873635
2001 An anti-apoptotic protein human survivin is a direct inhibitor of caspase-3 and -7. Biochemistry 568 11170436
2000 Regulation of apoptosis at cell division by p34cdc2 phosphorylation of survivin. Proceedings of the National Academy of Sciences of the United States of America 561 11069302
1994 Oligo-capping: a simple method to replace the cap structure of eukaryotic mRNAs with oligoribonucleotides. Gene 492 8125298
2003 Exploring the functional interactions between Aurora B, INCENP, and survivin in mitosis. Molecular biology of the cell 453 12925766
2000 Survivin and the inner centromere protein INCENP show similar cell-cycle localization and gene knockout phenotype. Current biology : CB 441 11084331
2004 The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC). Genome research 438 15489334
2022 OpenCell: Endogenous tagging for the cartography of human cellular organization. Science (New York, N.Y.) 432 35271311
2010 Systematic analysis of human protein complexes identifies chromosome segregation proteins. Science (New York, N.Y.) 421 20360068
2010 Two histone marks establish the inner centromere and chromosome bi-orientation. Science (New York, N.Y.) 397 20929775
2002 Inhibition of STAT3 signaling induces apoptosis and decreases survivin expression in primary effusion lymphoma. Blood 390 12393476
2017 Synergistic drug combinations for cancer identified in a CRISPR screen for pairwise genetic interactions. Nature biotechnology 378 28319085
2000 Livin, a novel inhibitor of apoptosis protein family member. The Journal of biological chemistry 372 11024045
2003 HBXIP functions as a cofactor of survivin in apoptosis suppression. The EMBO journal 367 12773388
1998 Induction of apoptosis and inhibition of cell proliferation by survivin gene targeting. The Journal of biological chemistry 367 9556606
2004 Borealin: a novel chromosomal passenger required for stability of the bipolar mitotic spindle. The Journal of cell biology 361 15249581
2004 The chromosomal passenger complex is required for chromatin-induced microtubule stabilization and spindle assembly. Cell 358 15260989
1999 Survivin-deltaEx3 and survivin-2B: two novel splice variants of the apoptosis inhibitor survivin with different antiapoptotic properties. Cancer research 332 10626797
2004 An IAP-IAP complex inhibits apoptosis. The Journal of biological chemistry 322 15218035
2003 Direct interaction between survivin and Smac/DIABLO is essential for the anti-apoptotic activity of survivin during taxol-induced apoptosis. The Journal of biological chemistry 315 12660240
2004 Mitochondrial survivin inhibits apoptosis and promotes tumorigenesis. The Journal of clinical investigation 309 15489959
2019 Survivin at a glance. Journal of cell science 285 30948431
2001 Cancer gene therapy using a survivin mutant adenovirus. The Journal of clinical investigation 281 11581299
2003 Regulation of survivin function by Hsp90. Proceedings of the National Academy of Sciences of the United States of America 271 14614132
2006 Structural, functional and therapeutic biology of survivin. Cancer letters 269 16621243
2005 Chromosome alignment and segregation regulated by ubiquitination of survivin. Science (New York, N.Y.) 209 16322459
2000 Human survivin is a kinetochore-associated passenger protein. The Journal of cell biology 207 11134084
2005 Role of survivin and its splice variants in tumorigenesis. British journal of cancer 189 15611788
2019 Cancer therapeutics using survivin BIRC5 as a target: what can we do after over two decades of study? Journal of experimental & clinical cancer research : CR 181 31439015
2001 Cytokine-regulated expression of survivin in myeloid leukemia. Blood 172 11313272
2006 Regulation of survivin expression by IGF-1/mTOR signaling. Oncogene 159 17072337
2021 BIRC3 and BIRC5: multi-faceted inhibitors in cancer. Cell & bioscience 156 33413657
2012 BIRC5/Survivin enhances aerobic glycolysis and drug resistance by altered regulation of the mitochondrial fusion/fission machinery. Oncogene 153 23146905
2008 New wirings in the survivin networks. Oncogene 150 18931693
2006 The case for Survivin as mitotic regulator. Current opinion in cell biology 150 16962308
2008 Cancer cells survive with survivin. Cancer science 149 18537980
2005 Survivin: a protein with dual roles in mitosis and apoptosis. International review of cytology 148 16344111
2004 Survivin: a bifunctional inhibitor of apoptosis protein. Veterinary pathology 148 15557069
2018 Therapeutic strategies involving survivin inhibition in cancer. Medicinal research reviews 131 30421440
2006 Survivin modulates microtubule dynamics and nucleation throughout the cell cycle. Molecular biology of the cell 129 16407408
2002 Expression of different survivin variants in gastric carcinomas: first clues to a role of survivin-2B in tumour progression. British journal of cancer 125 11875736
2002 Inhibitor of apoptosis protein survivin regulates vascular injury. Nature medicine 122 12172543
2014 Survivin and YM155: how faithful is the liaison? Biochimica et biophysica acta 118 24440709
2013 Treat cancers by targeting survivin: just a dream or future reality? Cancer treatment reviews 118 23453862
2012 Survivin is a therapeutic target in Merkel cell carcinoma. Science translational medicine 111 22572880
2011 Antisense inhibition of survivin expression as a cancer therapeutic. Molecular cancer therapeutics 93 21216939
2010 Regulation of survivin by PI3K/Akt/p70S6K1 pathway. Biochemical and biophysical research communications 91 20361940
2009 DNA methylation inhibits p53-mediated survivin repression. Oncogene 88 19363521
2006 Role of the Survivin gene in pathophysiology. The American journal of pathology 88 16816356
2008 Deconstructing Survivin: comprehensive genetic analysis of Survivin function by conditional knockout in a vertebrate cell line. The Journal of cell biology 83 18936249
2010 Acetylation directs survivin nuclear localization to repress STAT3 oncogenic activity. The Journal of biological chemistry 81 20826784
2007 Sp1 and Sp3 regulate basal transcription of the survivin gene. Biochemical and biophysical research communications 79 17350596
2003 Survivin: role in normal cells and in pathological conditions. Current cancer drug targets 77 12678716
1995 Xa receptor EPR-1. FASEB journal : official publication of the Federation of American Societies for Experimental Biology 76 7615156
2011 Knockdown of survivin (BIRC5) causes apoptosis in neuroblastoma via mitotic catastrophe. Endocrine-related cancer 72 21859926
2008 SPC3042: a proapoptotic survivin inhibitor. Molecular cancer therapeutics 71 18790754
2005 A survivin gene signature predicts aggressive tumor behavior. Cancer research 68 15867343
2015 The twisted survivin connection to angiogenesis. Molecular cancer 67 26584646
2014 MicroRNA regulation and therapeutic targeting of survivin in cancer. American journal of cancer research 67 25628918
2009 Runx2 regulates survivin expression in prostate cancer cells. Laboratory investigation; a journal of technical methods and pathology 64 19949374
2018 miR-203 inhibits ovarian tumor metastasis by targeting BIRC5 and attenuating the TGFβ pathway. Journal of experimental & clinical cancer research : CR 63 30241553
2009 Repression of BIRC5/survivin by FOXO3/FKHRL1 sensitizes human neuroblastoma cells to DNA damage-induced apoptosis. Molecular biology of the cell 63 19211844
2017 Survivin in autoimmune diseases. Autoimmunity reviews 62 28564620
2013 Transcriptional regulation of the survivin gene. Molecular biology reports 60 24197699
2007 Evaluation of survivin and NF-kappaB in psoriasis, an immunohistochemical study. Journal of cutaneous pathology 59 18005174
2011 Survivin: a dual player in healthy and diseased skin. The Journal of investigative dermatology 56 21900948
2014 Survivin beyond physiology: orchestration of multistep carcinogenesis and therapeutic potentials. Cancer letters 54 24560928
2011 Targeted BIRC5 silencing using YM155 causes cell death in neuroblastoma cells with low ABCB1 expression. European journal of cancer (Oxford, England : 1990) 54 22088485
2011 Investigations of survivin: the past, present and future. Frontiers in bioscience (Landmark edition) 52 21196211
2006 Survivin promoter polymorphism and cervical carcinogenesis. Journal of clinical pathology 50 16714396
2008 CCL2, survivin and autophagy: new links with implications in human cancer. Autophagy 49 18758234
2003 Expression of survivin protein in human colorectal carcinogenesis. World journal of gastroenterology 47 12717841
2002 Expression of the antiapoptosis gene survivin in human leukemia. International journal of hematology 47 11939262
2008 siRNA directed against survivin enhances pancreatic cancer cell gemcitabine chemosensitivity. Digestive diseases and sciences 45 18594980
2003 Upregulation of survivin by HIV-1 Vpr. Apoptosis : an international journal on programmed cell death 44 12510154
2019 Trace of survivin in cancer. European journal of cancer prevention : the official journal of the European Cancer Prevention Organisation (ECP) 43 29847456
2011 Endogenous knockdown of survivin improves chemotherapeutic response in ALL models. Leukemia 43 21844871
2011 Expression and function of survivin in canine osteosarcoma. Cancer research 41 22068035
2024 Survivin (BIRC5): Implications in cancer therapy. Life sciences 40 38848940
2017 Survivin and autoimmunity; the ins and outs. Immunology letters 39 29155234
2006 Expression of survivin and correlation with PCNA in osteosarcoma. Journal of surgical oncology 39 16705726
2021 Arsenic trioxide targets Hsp60, triggering degradation of p53 and survivin. Chemical science 38 34476069
2013 Survivin-induced abnormal ploidy contributes to cystic kidney and aneurysm formation. Circulation 36 24235270
2010 Survivin-T34A: molecular mechanism and therapeutic potential. OncoTargets and therapy 36 21289859
2004 Expression of survivin and its significance in colorectal cancer. World journal of gastroenterology 36 15334693
2004 Distinct dynamics of Aurora B and Survivin during mitosis. Cell cycle (Georgetown, Tex.) 36 15483398
2012 A novel role for survivin in erythroblast enucleation. Haematologica 35 22491741
2019 Potential Involvement of BIRC5 in Maintaining Pluripotency and Cell Differentiation of Human Stem Cells. Oxidative medicine and cellular longevity 32 30774747
2018 Epigenetic mechanism of survivin dysregulation in human cancer. Science China. Life sciences 32 29318497
2017 Enhanced expression of Survivin has distinct roles in adipocyte homeostasis. Cell death & disease 32 28055005
2017 Chromosomal instability induced by increased BIRC5/Survivin levels affects tumorigenicity of glioma cells. BMC cancer 32 29282022
2015 Survivin splice variants and their diagnostic significance. Tumour biology : the journal of the International Society for Oncodevelopmental Biology and Medicine 32 26245993
2011 The role of survivin for radiation oncology: moving beyond apoptosis inhibition. Current medicinal chemistry 32 21110807
2008 Survivin expression in renal cell carcinoma. Cancer investigation 32 19034775
2021 hnRNPA2B1 regulates the alternative splicing of BIRC5 to promote gastric cancer progression. Cancer cell international 29 34044823
2014 The emerging role of exosomes in survivin secretion. Histology and histopathology 29 25020159
2012 Implication of BIRC5 in asthma pathogenesis. International immunology 29 22336533
2014 Survivin safeguards chromosome numbers and protects from aneuploidy independently from p53. Molecular cancer 28 24886358
2004 Survivin and leukemia. International journal of hematology 28 15540897
2014 Down-regulation of survivin alleviates experimental arthritis. Journal of leukocyte biology 26 25381389
2015 An Old Flame Never Dies: Survivin in Cancer and Cellular Senescence. Gerontology 25 26159786
2013 HER2 stabilizes survivin while concomitantly down-regulating survivin gene transcription by suppressing Notch cleavage. The Biochemical journal 24 23323858
2006 Transcriptional expression of survivin and its splice variants in endometriosis. Molecular human reproduction 24 16644787
2020 The role of survivin in the progression of pancreatic ductal adenocarcinoma (PDAC) and a novel survivin-targeted therapeutic for PDAC. PloS one 23 31929540
2014 Overexpression of survivin and caspase 3 in oral carcinogenesis. Applied immunohistochemistry & molecular morphology : AIMM 23 23531848
2021 Mutant p53 regulates Survivin to foster lung metastasis. Genes & development 22 33737385
2009 Regulation of BIRC5 and its isoform BIRC5-2B in neuroblastoma. Cancer letters 22 19497660
2004 Survivin expression in acute leukemias and myelodysplastic syndromes. Leukemia & lymphoma 22 15512811
2020 BBOX1-AS1 Accelerates Gastric Cancer Proliferation by Sponging miR-3940-3p to Upregulate BIRC5 Expression. Digestive diseases and sciences 21 32394331
2019 Survivin modulatory role in autoimmune and autoinflammatory diseases. Journal of cellular physiology 21 31020660
2016 Reciprocal regulation of BMF and BIRC5 (Survivin) linked to Eomes overexpression in colorectal cancer. Cancer letters 21 27539959
2019 BIRC5 is a target for molecular imaging and detection of human pancreatic cancer. Cancer letters 20 31059751
2016 Targeting Survivin Enhances Chemosensitivity in Retinoblastoma Cells and Orthotopic Tumors. PloS one 20 27050416
2016 Survivin, a Promising Gene for Targeted Cancer Treatment. Asian Pacific journal of cancer prevention : APJCP 20 27644605
2021 CircANKRD52 Promotes the Tumorigenesis of Hepatocellular Carcinoma by Sponging miR-497-5p and Upregulating BIRC5 Expression. Cell transplantation 19 33845641
2006 HLA-A24 and survivin: possibilities in therapeutic vaccination against cancer. Journal of translational medicine 19 16948867
2012 Survivin in adrenocortical tumors - pathophysiological implications and therapeutic potential. Hormone and metabolic research = Hormon- und Stoffwechselforschung = Hormones et metabolisme 18 23143666
2014 Proteome analysis of a hepatocyte-specific BIRC5 (survivin)-knockout mouse model during liver regeneration. Journal of proteome research 16 24818710
2024 TRAF4 regulates ubiquitination-modulated survivin turnover and confers radioresistance. International journal of biological sciences 15 38164179
2020 Downregulation of TRIM27 suppresses gastric cancer cell proliferation via inhibition of the Hippo-BIRC5 pathway. Pathology, research and practice 15 32825933