Affinage

BIRC5

Baculoviral IAP repeat-containing protein 5 · UniProt O15392

Length
142 aa
Mass
16.4 kDa
Annotated
2026-06-09
100 papers in source corpus 24 papers cited in narrative 24 extracted findings
Cross-family judge vs UniProt: Affinage preferred faithfulness: 7/7 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

BIRC5 (survivin) is a dual-function mitotic regulator and apoptosis suppressor that operates principally as an essential subunit of the chromosomal passenger complex (CPC) alongside Aurora B, Borealin, and INCENP, where it dictates CPC localization to centromeres and is required for proper chromosome segregation and cytokinesis (PMID:16962308). Centromere targeting is achieved through a leucine-rich CRM1-binding nuclear export signal that tethers the CPC and is concurrently required for survivin's cytoprotective activity (PMID:17361097), while dynamic centromere association is controlled by a degradation-independent Lys63 ubiquitination/deubiquitination cycle in which Ufd1-mediated Lys63 ubiquitination promotes association and hFAM-mediated deubiquitination drives dissociation (PMID:16322459). Within the CPC, PLK1 phosphorylates survivin at Ser20 as a priming event required for Aurora B activation and correct spindle-microtubule attachment (PMID:21148584), and survivin additionally modulates microtubule dynamics directly, independently of Aurora B, by suppressing centrosomal microtubule nucleation and catastrophe (PMID:16407408). Loss of survivin produces merotelic kinetochore attachments, polyploidy, and a DNA damage response, establishing it as essential for amphitelic kinetochore-spindle assembly and genomic stability (PMID:24886358). Beyond mitosis, survivin suppresses apoptosis: its stability and antiapoptotic function depend on an Hsp90 ATPase-domain/survivin BIR-domain interaction whose disruption triggers proteasomal degradation and mitochondrial apoptosis (PMID:14614132), and it reprograms metabolism by recruiting DRP1 to drive mitochondrial fragmentation, inhibiting respiratory complex I, repressing Bim, and shifting cells toward aerobic glycolysis (PMID:23146905). Survivin also negatively regulates autophagy to protect genome integrity, with its knockdown inducing autophagy-dependent ROS, DNA damage, and downregulation of homologous-recombination factors (PMID:33549731). Its expression is governed by Sp1/Sp3 at a GC-rich TATA-less promoter (PMID:17350596), by E2F factors (PMID:19497660), and by the PI3K/Akt/p70S6K1 axis (PMID:20361940), and a gain-of-function mutant p53–YAP complex induces BIRC5 to promote metastasis (PMID:33737385).

Mechanistic history

Synthesis pass · year-by-year structured walk · 24 steps
  1. 1999 Medium

    Established that survivin exists as functionally distinct splice isoforms, showing that structural changes in the BIR domain alter antiapoptotic capacity.

    Evidence Northern blot, RT-PCR and transfection assays in renal cell carcinoma lines identifying survivin-deltaEx3 and survivin-2B

    PMID:10626797

    Open questions at the time
    • Does not define the molecular mechanism by which BIR-domain alterations change antiapoptotic activity
    • Physiological abundance and roles of the isoforms unresolved
  2. 2000 Medium

    Linked survivin to cell cycle progression by showing it engages CDK4 and liberates p21 to promote S-phase entry, framing survivin as more than a passive apoptosis inhibitor.

    Evidence Co-immunoprecipitation and cell cycle analysis after survivin transfection in hepatocellular carcinoma cells

    PMID:10796883

    Open questions at the time
    • Single-lab Co-IP without reciprocal mapping
    • Direct vs indirect nature of the CDK4 interaction not resolved
  3. 2003 High

    Defined a chaperone dependency for survivin stability, showing the Hsp90 ATPase domain binds the survivin BIR domain to prevent proteasomal degradation and apoptosis.

    Evidence Reciprocal Co-IP with domain mapping, antibody-mediated disruption, proteasome rescue, apoptosis and mitosis assays

    PMID:14614132

    Open questions at the time
    • Does not identify the E3 ligase acting on uncomplexed survivin
    • Structural basis of the BIR–ATPase interaction not solved
  4. 2003 Medium

    Connected viral cell-cycle manipulation to survivin transcription, showing HIV-1 Vpr transactivates the survivin promoter contingent on G2/M arrest.

    Evidence Survivin promoter reporter assays with Vpr expression and G2/M arrest blockade

    PMID:12510154

    Open questions at the time
    • Promoter element mediating cell-cycle-dependent activation not mapped
    • Reporter-based, not endogenous locus
  5. 2005 High

    Revealed a non-proteolytic ubiquitin code controlling survivin's centromere residency, distinguishing Lys63 ubiquitination/deubiquitination from degradative Lys48 signaling.

    Evidence Biochemical ubiquitination assays, siRNA of hFAM and Ufd1, live imaging and chromosome segregation readouts

    PMID:16322459

    Open questions at the time
    • How the ubiquitin cycle is spatially timed at centromeres unresolved
    • Other deubiquitinases/ligases not excluded
  6. 2006 High

    Separated a CPC-independent activity of survivin, demonstrating it directly modulates microtubule nucleation and catastrophe rather than acting solely through Aurora B.

    Evidence siRNA depletion and overexpression with time-lapse imaging of GFP-tubulin/EB1 and pharmacologic Aurora B inhibition

    PMID:16407408

    Open questions at the time
    • Molecular basis of direct microtubule modulation not defined
    • Whether monomeric or complexed survivin mediates this is unclear
  7. 2006 High

    Consolidated survivin's identity as an evolutionarily conserved CPC subunit that dictates centromere localization and is essential for segregation and cytokinesis.

    Evidence Synthesis of Co-IP, localization and genetic knockdown studies across species

    PMID:16962308

    Open questions at the time
    • Review-level synthesis rather than a single primary dataset
    • Stoichiometry and assembly order within the CPC not detailed here
  8. 2007 Medium

    Identified the CRM1-binding nuclear export signal as the determinant linking centromere targeting to cytoprotection, unifying mitotic and antiapoptotic functions.

    Evidence NES identification, CRM1 interaction and export-deficient mutant analysis with viability assays

    PMID:17361097

    Open questions at the time
    • Limited methodological detail; single lab
    • How export status mechanistically alters apoptosis protection not dissected
  9. 2007 Medium

    Mapped the basal transcriptional control of BIRC5 to Sp1/Sp3 acting through defined GC-box elements in a TATA-less promoter.

    Evidence Promoter cloning, EMSA, RNAi of Sp1/Sp3, mithramycin treatment and luciferase reporters

    PMID:17350596

    Open questions at the time
    • Does not address inducible/context-specific regulation
    • Combinatorial control with other factors not tested
  10. 2009 Medium

    Explained survivin de-repression in cancer epigenetically, showing CpG-island methylation blocks p53 binding and thus relieves p53-mediated repression.

    Evidence Methylation-specific PCR, pyrosequencing, decitabine demethylation and p53 binding assays

    PMID:19363521

    Open questions at the time
    • Direct p53 occupancy change at the locus inferred pharmacologically
    • Cell-context dependence of p53 repression not surveyed
  11. 2010 Medium

    Placed survivin downstream of growth-factor signaling by establishing the PI3K/Akt/p70S6K1 axis as a controller of its mRNA, with p70S6K1 sufficient for induction.

    Evidence Overexpression of active PI3K/Akt/PTEN/p70S6K1, rapamycin treatment and mRNA quantification

    PMID:20361940

    Open questions at the time
    • Transcriptional vs stability contribution to mRNA change not separated
    • Direct effector at the promoter not identified
  12. 2010 High

    Defined the kinase trigger of survivin's mitotic function, showing PLK1 phosphorylation at Ser20 primes Aurora B activation and correct kinetochore attachment.

    Evidence In vitro PLK1 kinase assay, S20A phospho-dead mutant, FRET Aurora B activity reporter and live mitosis imaging

    PMID:21148584

    Open questions at the time
    • How Ser20 phosphorylation structurally activates Aurora B unresolved
    • Phosphatase reversing Ser20 not identified
  13. 2012 High

    Uncovered a metabolic arm of survivin's antiapoptotic role, showing it recruits DRP1 to fragment mitochondria, inhibits complex I, and drives aerobic glycolysis.

    Evidence Gain/loss of function in neuroblastoma with mitochondrial imaging, respiration, ROS and glycolysis-inhibitor assays

    PMID:23146905

    Open questions at the time
    • Direct vs indirect DRP1 recruitment mechanism not resolved
    • Whether this occurs in non-cancer cells unaddressed
  14. 2013 Medium

    Extended transcriptional control of BIRC5 to E2F/MYCN networks and added CDC2 phosphorylation as a post-translational stability mechanism in neuroblastoma.

    Evidence E2F reporter/ChIP, CDC2 siRNA, protein stability assays and tumor sample analysis

    PMID:19497660

    Open questions at the time
    • CDC2 phospho-site on survivin not mapped here
    • Relative weight of E2F vs MYCN inputs unresolved
  15. 2013 Medium

    Showed that oncogenic HER2 stabilizes survivin protein via Akt/CDK1-cyclin B1 phosphorylation at Thr34 while limiting its ubiquitination, integrating receptor signaling with survivin abundance.

    Evidence HER2 overexpression, Thr34 mutagenesis, pathway inhibitors, XAF1 knockdown and ubiquitination assays

    PMID:23323858

    Open questions at the time
    • Multiple parallel mechanisms not quantitatively ranked
    • Direct kinase–substrate contacts not validated in vitro
  16. 2013 Medium

    Connected stemness factor OCT4 to BIRC5 induction, demonstrating an indirect promoter-activating route and therapeutic synergy of co-suppression.

    Evidence OCT4 gain/loss, BIRC5 promoter reporters, CCND1 ChIP, apoptosis assays and xenografts

    PMID:23433354

    Open questions at the time
    • Mediator bridging OCT4 to the BIRC5 promoter not identified
    • Direct vs indirect remains formally open
  17. 2013 Medium

    Demonstrated a survivin role in inflammatory/immune contexts, linking its downregulation to reduced invasiveness and altered T-cell differentiation via Blimp-1.

    Evidence Lentiviral shRNA in two mouse arthritis models with metalloproteinase, β-catenin/vimentin and T-cell assays

    PMID:25381389

    Open questions at the time
    • Direct molecular targets of survivin in T cells not defined
    • Cell-intrinsic vs extrinsic effects not separated
  18. 2014 High

    Established survivin as essential for amphitelic kinetochore-spindle assembly and genome stability, with depletion causing merotely, polyploidy and DDR independent of p53 status.

    Evidence Stable RNAi in isogenic p53 WT/null lines, spectral karyotyping, microscopy and ATM/DNA-PK inhibition

    PMID:24886358

    Open questions at the time
    • Mechanistic step at which merotely arises not pinpointed
    • Contribution of CPC vs direct microtubule roles not separated
  19. 2015 Medium

    Identified a therapeutically exploitable degradation route, showing glycolysis inhibition triggers PINK1/Parkin-mediated autophagic degradation of survivin, releasing Beclin-1 to enhance death.

    Evidence 2DG treatment, Parkin knockdown, Beclin-1 Co-IP, xenografts and mitochondrial imaging

    PMID:26148234

    Open questions at the time
    • Direct Parkin-survivin ubiquitination not demonstrated
    • Generality beyond survivin-overexpressing neuroblastoma unknown
  20. 2017 Medium

    Revealed a metabolic-hormonal function in adipocytes, where survivin suppresses lipolysis via Adrb3/cAMP downregulation and Fsp27 stabilization, downstream of insulin/PI3K/mTOR.

    Evidence Ectopic overexpression in adipocyte lines with cAMP, Fsp27 stability, lipolysis assays and pathway inhibitors

    PMID:28055005

    Open questions at the time
    • In vivo adipose relevance not established
    • Mechanism of Adrb3 downregulation unresolved
  21. 2018 Medium

    Localized survivin to the cancer cell surface and validated it as an extracellular antibody target with in vivo antitumor efficacy.

    Evidence Flow cytometry/immunofluorescence for surface survivin and antibody treatment in glioma and melanoma models

    PMID:29540489

    Open questions at the time
    • Mechanism of survivin externalization/membrane association unknown
    • Surface partner anchoring it not identified
  22. 2018 Medium

    Assigned a function to extracellular survivin, showing exosomal survivin promotes recipient-cell exosome internalization.

    Evidence Exosome uptake tracking with survivin blocking and receptor inhibition

    PMID:30405884

    Open questions at the time
    • Direct interaction of exosomal survivin with named receptors not shown
    • Single-lab pharmacologic evidence
  23. 2021 Medium

    Defined survivin as a negative regulator of autophagy protecting genome integrity, with its loss inducing autophagy-dependent ROS, DNA damage and HR-factor downregulation.

    Evidence BIRC5 and RAD54L/RAD51 siRNA across multiple cell lines with ROS, γH2AX and autophagic vesicle imaging

    PMID:33549731

    Open questions at the time
    • Direct molecular link from survivin to autophagy machinery not mapped
    • Causal ordering of ROS vs DNA damage not fully resolved
  24. 2021 High

    Established a gain-of-function oncogenic axis, showing mutant p53 binds YAP to induce BIRC5 and drive metastasis, distinct from wild-type p53 behavior.

    Evidence Co-IP of mutant p53–YAP, RNA-seq, tail-vein lung metastasis model with survivin depletion rescue

    PMID:33737385

    Open questions at the time
    • Direct mutant p53–YAP occupancy at the BIRC5 promoter not shown
    • Downstream survivin effectors driving metastasis not defined

Open questions

Synthesis pass · forward-looking unresolved questions
  • How survivin's distinct molecular pools — CPC-bound mitotic, mitochondrial/metabolic, autophagy-regulating, and surface/exosomal — are partitioned and coordinated within a single cell remains unresolved.
  • No unifying structural model links the BIR domain, NES, and post-translational marks to functional pool selection
  • Mechanism of survivin externalization to the cell surface and exosomes is unknown
  • Direct effectors of the metabolic and autophagy functions not fully identified

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0098772 molecular function regulator activity 3 GO:0060090 molecular adaptor activity 2 GO:0008092 cytoskeletal protein binding 1
Localization
GO:0005694 chromosome 2 GO:0005634 nucleus 1 GO:0005739 mitochondrion 1 GO:0005815 microtubule organizing center 1 GO:0005886 plasma membrane 1
Pathway
R-HSA-1640170 Cell Cycle 4 R-HSA-74160 Gene expression (Transcription) 4 R-HSA-5357801 Programmed Cell Death 2 R-HSA-9612973 Autophagy 2 R-HSA-1430728 Metabolism 1
Partners
AURKBCDK4CRM1DNM1LHSP90INCENPTP53YAP1
Complex memberships
chromosomal passenger complex (CPC)

Evidence

Reading pass · 24 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
1999 Two novel splice variants of survivin were identified: survivin-deltaEx3 (lacking exon 3) and survivin-2B (retaining part of intron 2 as a cryptic exon). Both cause structural changes in the BIR domain. In transfection experiments, survivin-deltaEx3 retained antiapoptotic properties while survivin-2B showed markedly reduced antiapoptotic potential. Northern blot, RT-PCR, transfection assays in renal cell carcinoma cell lines Cancer research Medium 10626797
2000 Survivin interacts with cyclin-dependent kinase 4 (CDK4), and overexpression of survivin releases p21(WAF1/Cip1) from CDK4, thereby promoting cell cycle progression (decrease in G0/G1, increase in S phase) in hepatocellular carcinoma cells. Co-immunoprecipitation, cell cycle analysis after survivin transfection, immunofluorescence Hepatology Medium 10796883
2003 Hsp90 associates with survivin via an interaction involving the ATPase domain of Hsp90 and the survivin BIR domain. Disruption of this complex (by global Hsp90 inhibition or antibody-mediated targeting) causes proteasomal degradation of survivin, mitochondrial-dependent apoptosis, and mitotic defects. Co-immunoprecipitation, antibody-mediated complex disruption, proteasome inhibitor rescue, cell death and mitosis assays Proceedings of the National Academy of Sciences of the United States of America High 14614132
2005 Survivin is ubiquitinated in mitosis through both Lys48 and Lys63 ubiquitin linkages. The deubiquitinating enzyme hFAM mediates Lys63 deubiquitination required for dissociation of survivin from centromeres, while Lys63 ubiquitination mediated by Ufd1 is required for association of survivin with centromeres. This ubiquitination cycle regulates chromosome alignment and segregation independently of protein degradation. Biochemical ubiquitination assays, siRNA knockdown of hFAM and Ufd1, live-cell imaging, chromosome segregation assays Science High 16322459
2006 Depletion of survivin by siRNA increased centrosomal microtubule nucleation and increased microtubule catastrophe frequency, whereas survivin overexpression reduced centrosomal microtubule nucleation and suppressed microtubule dynamics in mitotic spindles and midbodies. This effect was specific to survivin and not recapitulated by Aurora B depletion, indicating survivin directly modulates microtubule dynamics. siRNA depletion, time-lapse imaging of GFP-alpha-tubulin and GFP-EB1, pharmacologic Aurora B inhibition Molecular biology of the cell High 16407408
2006 Survivin acts as a subunit of the chromosomal passenger complex (CPC), together with Aurora B kinase, Borealin, and INCENP. Within this complex, survivin dictates CPC localization to centromeres and is essential for proper chromosome segregation and cytokinesis. This mitotic regulatory function is conserved throughout evolution. Review/synthesis citing multiple experimental studies (Co-IP, localization, genetic knockdown) Current opinion in cell biology High 16962308
2007 The nuclear export receptor CRM1 interacts with a leucine-rich nuclear export signal (NES) conserved in all mammalian survivin proteins, tethering the CPC to the centromere. Export-deficient survivin fails to protect tumor cells against apoptosis, indicating the CRM1/survivin interaction is required for both centromere localization and cytoprotective activity. Identification of NES by sequence analysis, CRM1 interaction assays, export-deficient mutant analysis, cell viability assays Cell cycle Medium 17361097
2007 Sp1 and Sp3 transcription factors regulate basal survivin promoter activity. Two Sp1-binding sites within the proximal 269 bp GC-rich, TATA-less promoter (at positions -148 to -153 and -127 to -140) are essential. Both Sp1 and Sp3 activate the survivin promoter, as shown by EMSA, RNAi knockdown of Sp1/Sp3, mithramycin treatment, and overexpression. Promoter cloning, EMSA, RNAi knockdown, mithramycin treatment, Sp1/Sp3 overexpression, luciferase reporter assays Biochemical and biophysical research communications Medium 17350596
2009 DNA methylation of the survivin CpG island inhibits p53 binding to the survivin promoter, thereby preventing p53-mediated repression of survivin. Demethylation by decitabine restores p53-dependent survivin repression. This represents a mechanism of survivin de-repression via promoter methylation blocking a transcriptional repressor. Methylation-specific PCR, pyrosequencing, decitabine treatment, p53 binding assays, microarray analysis Oncogene Medium 19363521
2010 PLK1 (polo-like kinase 1) phosphorylates survivin at Ser20, a priming phosphorylation required for Aurora B kinase activation within the CPC. Inhibition of PLK1 or expression of non-phosphorylatable survivin (S20A mutant) prevents Aurora B activation and correct spindle microtubule attachment, leading to chromosome segregation errors. PLK1 kinase assays, survivin S20A phospho-dead mutant expression, FRET-based Aurora B activity reporter, quantitative phosphorylation assays, live-cell mitosis imaging Journal of molecular cell biology High 21148584
2010 The PI3K/Akt/p70S6K1 signaling pathway regulates survivin mRNA expression. Overexpression of activated PI3K or Akt induces survivin mRNA, while PTEN overexpression decreases it. p70S6K1 alone is sufficient to induce survivin expression, and rapamycin treatment decreases survivin mRNA, placing p70S6K1 as a key downstream effector. Overexpression of active PI3K (v-P3k), wild-type and mutant PTEN, p70S6K1; rapamycin treatment; survivin siRNA; mRNA quantification Biochemical and biophysical research communications Medium 20361940
2012 Survivin induces mitochondrial fragmentation by recruiting the fission regulator DRP1/DNM1L to mitochondria, inhibits mitochondrial respiratory complex I (preventing ROS accumulation and FOXO3-induced apoptosis), represses BCL2L11/Bim expression, and shifts cells from oxidative phosphorylation to aerobic glycolysis. Glycolysis inhibitors neutralize the antiapoptotic effect of survivin. Survivin overexpression/knockdown in neuroblastoma cells, mitochondrial imaging, mitochondrial respiration assays, ROS measurement, glycolysis inhibitor treatment, DRP1 localization by fractionation/imaging Oncogene High 23146905
2013 OCT4 upregulates BIRC5 expression indirectly by increasing BIRC5 promoter activity (no direct OCT4 binding site in BIRC5 promoter), while directly binding an octamer motif in the CCND1 promoter to upregulate cyclin D1. Co-suppression of OCT4 and BIRC5 induces apoptosis and cell cycle arrest in HCC cells and suppresses xenograft growth. OCT4 overexpression/knockdown, BIRC5 promoter luciferase reporter assays, ChIP for CCND1 promoter, apoptosis assays, xenograft mouse model BMC cancer Medium 23433354
2013 HER2 stabilizes survivin protein by activating the HER2/Akt/CDK1-cyclin B1 pathway, which phosphorylates survivin at Thr34, the most important residue for survivin stability. Simultaneously, HER2/ERK signaling downregulates γ-secretase activity, reducing Notch cleavage and Notch-dependent survivin transcription. ERK also decreases XAF1, reducing the XIAP-XAF1 E3 ligase complex that ubiquitinates survivin. HER2 overexpression, Thr34 mutagenesis, pathway inhibitor treatments, XAF1 knockdown, ubiquitination assays The Biochemical journal Medium 23323858
2014 Survivin knockdown causes polyploidization, merotelic kinetochore-spindle assemblies, γH2AX foci, and DNA damage response (DDR) with transient p53-mediated G1 arrest in p53 wild-type cells. Chromosomal aberrations indicative of NHEJ-based DSB repair occur only in survivin-depleted cells. These effects are independent of p53 status, establishing survivin as essential for amphitelic kinetochore-spindle assembly. Stable RNAi knockdown in isogenic p53 WT and p53-null cell lines, spectral karyotyping, confocal microscopy, western blot, proliferation assays, ATM/DNA-PK inhibition Molecular cancer High 24886358
2015 Glycolysis inhibitor 2-deoxy-D-glucose (2DG) selectively acts on survivin-overexpressing neuroblastoma cells by inducing autophagic degradation of survivin via activation of the E3-ubiquitin ligase Parkin (a downstream target of PINK1). Survivin degradation releases bound Beclin-1, enhancing autophagy and cell death. Parkin knockdown reduces sensitivity of survivin-expressing cells to glycolysis inhibition. 2DG treatment, Parkin knockdown, Beclin-1 co-immunoprecipitation, xenograft mouse model, mitochondrial network imaging Oncogene Medium 26148234
2013 BIRC5 is a direct transcriptional target of activating E2F transcription factors in neuroblastoma, primarily when p21Cip1 and p27Kip1 are suppressed. MYCN indirectly induces BIRC5 by suppressing CDKN1A/p21Cip1 and inducing Skp2 (which promotes p27Kip1 degradation). CDC2 phosphorylates BIRC5 to increase its protein stability; selective CDC2 knockdown inhibits BIRC5 abundance and antiapoptotic activity. E2F overexpression/reporter assays, CDC2 siRNA knockdown, ChIP, protein stability assays, neuroblastoma tumor samples Cancer letters Medium 19497660
2018 Survivin is present on the outer cell membrane of a wide variety of cancer cell types (murine and human glioma, melanoma). Anti-survivin monoclonal antibodies generated against a survivin immunogen display antitumor activity in vivo against murine GL261 gliomas (flank and intracranial) and B16 melanoma, beyond CD8-mediated lysis. Flow cytometry and immunofluorescence for cell-surface survivin, in vivo tumor models with antibody treatment, immune serum analysis Clinical cancer research Medium 29540489
2018 Exosomal survivin facilitates exosome internalization by recipient cancer cells. Blocking exosomal survivin reduces exosome uptake. Membrane receptors transferrin receptor, endothelin B receptor, insulin receptor alpha, and membrane glucocorticoid receptor all facilitate exosomal internalization. Exosome isolation, PKH67 lipophilic staining, immunofluorescence, flow cytometry, receptor blocking experiments Oncotarget Medium 30405884
2021 BIRC5 downregulation (by siRNA) induces autophagy-dependent ROS production that causes DNA damage/strand breaks, and concurrently downregulates RAD54L, RAD51, and MRE11 (homologous recombination factors). Autophagic vesicles form proximal to the nucleus and trigger DNA leakage, revealing survivin as an autophagy negative-modulator that protects genome stability. BIRC5 siRNA in MCF7, MDA-MB-231, SK-BR-3, and MEF cells; RAD54L/RAD51 siRNA; ROS measurement; DNA damage assays (γH2AX); autophagic vesicle imaging Pharmacological research Medium 33549731
2021 Mutant p53 (Trp53R172H) binds YAP in esophageal squamous cell carcinoma cells, and this complex induces Survivin (BIRC5) expression. Depletion of Survivin specifically decreases mutant p53-driven lung metastasis in a tail-vein injection model. Wild-type p53 does not bind YAP, establishing a gain-of-function mutant p53–YAP–BIRC5 axis in metastasis. shRNA depletion of Trp53R172H, Co-IP for mutant p53–YAP interaction, bulk RNA-seq, tail-vein lung metastasis mouse model, survivin depletion rescue experiment Genes & development High 33737385
2013 Survivin downregulation reduces metalloproteinases, β-catenin, and vimentin, limiting synovial invasive capacity in experimental arthritis. The inhibition leads to p53-independent reduction of T cell proliferation and favors Blimp-1 transcription and activity, limiting IL-2 production and facilitating regulatory Foxp3+CD4+ and effector CD8+ T cells. Lentivirus shRNA knockdown of survivin in mouse arthritis models (mBSA-induced and collagen type II-induced), metalloproteinase assays, β-catenin/vimentin western blot, T cell proliferation and differentiation assays Journal of leukocyte biology Medium 25381389
2017 Survivin overexpression in mature adipocytes downregulates Adrb3 (reducing cAMP production), upregulates Fsp27 protein (via reduced degradation), and inhibits isoproterenol-stimulated lipolysis. Survivin expression in adipocytes is induced by insulin through the PI3K/mTOR pathway and is suppressed by starvation. Ectopic survivin overexpression in 3T3-L1 and C3H10T1/2 cells, cAMP measurement, Fsp27 protein stability assays, lipolysis assays, PI3K/mTOR inhibitor treatment Cell death & disease Medium 28055005
2003 HIV-1 Vpr protein upregulates survivin expression via survivin promoter transactivation, dependent on Vpr-induced G2/M cell cycle arrest. Blocking Vpr-induced G2/M arrest eliminates survivin promoter transactivation, linking cell cycle position to survivin transcriptional regulation. Survivin promoter reporter assays, Vpr expression, G2/M arrest inhibition experiments Apoptosis Medium 12510154

Source papers

Stage 0 corpus · 100 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2016 Survivin: a unique target for tumor therapy. Cancer cell international 350 27340370
1999 Survivin-deltaEx3 and survivin-2B: two novel splice variants of the apoptosis inhibitor survivin with different antiapoptotic properties. Cancer research 333 10626797
2000 Survivin promotes cell proliferation in human hepatocellular carcinoma. Hepatology (Baltimore, Md.) 307 10796883
2019 Survivin at a glance. Journal of cell science 288 30948431
2003 Survivin study: what is the next wave? Journal of cellular physiology 275 12942537
2003 Regulation of survivin function by Hsp90. Proceedings of the National Academy of Sciences of the United States of America 272 14614132
2006 Structural, functional and therapeutic biology of survivin. Cancer letters 269 16621243
2015 Survivin: A molecular biomarker in cancer. The Indian journal of medical research 256 26112839
2007 Survivin: a promising tumor biomarker. Cancer letters 214 17275177
2005 Chromosome alignment and segregation regulated by ubiquitination of survivin. Science (New York, N.Y.) 209 16322459
2005 Survivin as a target for new anticancer interventions. Journal of cellular and molecular medicine 207 15963255
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 184 31439015
2001 Cytokine-regulated expression of survivin in myeloid leukemia. Blood 172 11313272
2021 BIRC3 and BIRC5: multi-faceted inhibitors in cancer. Cell & bioscience 158 33413657
2008 Targeting survivin in cancer therapy. Expert opinion on therapeutic targets 155 18348682
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
2014 Survivin as a preferential target for cancer therapy. International journal of molecular sciences 144 24531137
2011 Survivin expression and targeting in breast cancer. Surgical oncology 138 21334875
2018 Therapeutic strategies involving survivin inhibition in cancer. Medicinal research reviews 133 30421440
2015 Survivin - The inconvenient IAP. Seminars in cell & developmental biology 132 25591986
2006 Survivin modulates microtubule dynamics and nucleation throughout the cell cycle. Molecular biology of the cell 129 16407408
2003 Survivin and apoptosis control. Advances in cancer research 120 12665052
2014 Survivin and YM155: how faithful is the liaison? Biochimica et biophysica acta 119 24440709
2013 Treat cancers by targeting survivin: just a dream or future reality? Cancer treatment reviews 118 23453862
2021 Kidney cancer biomarkers and targets for therapeutics: survivin (BIRC5), XIAP, MCL-1, HIF1α, HIF2α, NRF2, MDM2, MDM4, p53, KRAS and AKT in renal cell carcinoma. Journal of experimental & clinical cancer research : CR 95 34384473
2010 Regulation of survivin by PI3K/Akt/p70S6K1 pathway. Biochemical and biophysical research communications 92 20361940
2015 Survivin in survival of hepatocellular carcinoma. Cancer letters 91 26118774
2010 Aurora B kinase activation requires survivin priming phosphorylation by PLK1. Journal of molecular cell biology 88 21148584
2009 DNA methylation inhibits p53-mediated survivin repression. Oncogene 88 19363521
2007 Sp1 and Sp3 regulate basal transcription of the survivin gene. Biochemical and biophysical research communications 79 17350596
2002 Survivin--a universal tumor antigen. Histology and histopathology 79 11962766
2003 Survivin: role in normal cells and in pathological conditions. Current cancer drug targets 77 12678716
2012 Survivin signaling in clinical oncology: a multifaceted dragon. Medicinal research reviews 73 22688671
2004 Proliferation, apoptosis, and survivin expression in keratinocytic neoplasms and hyperplasias. The American Journal of dermatopathology 73 15166502
2013 OCT4 increases BIRC5 and CCND1 expression and promotes cancer progression in hepatocellular carcinoma. BMC cancer 72 23433354
2015 The twisted survivin connection to angiogenesis. Molecular cancer 68 26584646
2005 A survivin gene signature predicts aggressive tumor behavior. Cancer research 68 15867343
2014 MicroRNA regulation and therapeutic targeting of survivin in cancer. American journal of cancer research 67 25628918
2015 BIRC5/Survivin as a target for glycolysis inhibition in high-stage neuroblastoma. Oncogene 66 26148234
2018 miR-203 inhibits ovarian tumor metastasis by targeting BIRC5 and attenuating the TGFβ pathway. Journal of experimental & clinical cancer research : CR 63 30241553
2019 Toward early cancer detection: Focus on biosensing systems and biosensors for an anti-apoptotic protein survivin and survivin mRNA. Biosensors & bioelectronics 62 31078841
2017 Survivin in autoimmune diseases. Autoimmunity reviews 62 28564620
2013 Transcriptional regulation of the survivin gene. Molecular biology reports 61 24197699
2007 Survivin's dual role: an export's view. Cell cycle (Georgetown, Tex.) 61 17361097
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 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
2003 Expression of survivin protein in human colorectal carcinogenesis. World journal of gastroenterology 47 12717841
2024 Survivin (BIRC5): Implications in cancer therapy. Life sciences 46 38848940
2010 Survivin: a target from brain cancer to neurodegenerative disease. Critical reviews in biochemistry and molecular biology 46 20925597
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
2015 Survivin expression and serum levels in pancreatic cancer. World journal of surgical oncology 43 26016480
2011 Expression and function of survivin in canine osteosarcoma. Cancer research 41 22068035
2010 Targeting survivin in cancer: patent review. Expert opinion on therapeutic patents 40 21083520
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
2018 Survivin Monoclonal Antibodies Detect Survivin Cell Surface Expression and Inhibit Tumor Growth In Vivo. Clinical cancer research : an official journal of the American Association for Cancer Research 38 29540489
2007 IAP survivin regulates atherosclerotic macrophage survival. Arteriosclerosis, thrombosis, and vascular biology 37 17255535
2013 Survivin-induced abnormal ploidy contributes to cystic kidney and aneurysm formation. Circulation 36 24235270
2004 Expression of survivin and its significance in colorectal cancer. World journal of gastroenterology 36 15334693
2019 Ovarian Primary and Metastatic Tumors Suppressed by Survivin Knockout or a Novel Survivin Inhibitor. Molecular cancer therapeutics 35 31515295
2019 Potential Involvement of BIRC5 in Maintaining Pluripotency and Cell Differentiation of Human Stem Cells. Oxidative medicine and cellular longevity 33 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
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
2014 Survivin safeguards chromosome numbers and protects from aneuploidy independently from p53. Molecular cancer 29 24886358
2014 The emerging role of exosomes in survivin secretion. Histology and histopathology 29 25020159
2004 Survivin and leukemia. International journal of hematology 28 15540897
2022 Survivin in Breast Cancer: A Review. Genetic testing and molecular biomarkers 27 36166738
2014 Down-regulation of survivin alleviates experimental arthritis. Journal of leukocyte biology 26 25381389
2011 Survivin and pancreatic cancer. World journal of clinical oncology 26 21611091
2020 BIRC5/Survivin Expression as a Non-Invasive Biomarker of Endometriosis. Diagnostics (Basel, Switzerland) 25 32751449
2015 An Old Flame Never Dies: Survivin in Cancer and Cellular Senescence. Gerontology 25 26159786
2006 Survivin: an inhibitor of apoptosis in pediatric cancer. Pediatric blood & cancer 25 16534789
2021 Survivin and caspases serum protein levels and survivin variants mRNA expression in sepsis. Scientific reports 24 33441606
2021 YM155 and BIRC5 downregulation induce genomic instability via autophagy-mediated ROS production and inhibition in DNA repair. Pharmacological research 24 33549731
2013 HER2 stabilizes survivin while concomitantly down-regulating survivin gene transcription by suppressing Notch cleavage. The Biochemical journal 24 23323858
2009 Differential expression of survivin and its splice variants, survivin-DeltaEx3 and survivin-2B, in bladder cancer. Cancer detection and prevention 24 19186007
2006 Transcriptional expression of survivin and its splice variants in endometriosis. Molecular human reproduction 24 16644787
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
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
2021 CircANKRD52 Promotes the Tumorigenesis of Hepatocellular Carcinoma by Sponging miR-497-5p and Upregulating BIRC5 Expression. Cell transplantation 20 33845641
2020 Survivin modulation in the antimelanoma activity of prodiginines. European journal of pharmacology 20 32814079
2016 Survivin, a Promising Gene for Targeted Cancer Treatment. Asian Pacific journal of cancer prevention : APJCP 20 27644605
2011 Survivin in skin pathologies. Experimental dermatology 20 21585553
2020 Targeting survivin sensitizes cervical cancer cells to radiation treatment. Bioengineered 19 31959045
2018 Exosomal survivin facilitates vesicle internalization. Oncotarget 19 30405884

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