Affinage

CASP3

Caspase-3 · UniProt P42574

Length
277 aa
Mass
31.6 kDa
Annotated
2026-06-09
100 papers in source corpus 34 papers cited in narrative 33 extracted findings
Cross-family judge vs UniProt: Affinage preferred faithfulness: 6/6 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

CASP3 (CPP32/Yama/apopain) is the principal executioner cysteine protease of apoptosis, synthesized as a 32-kDa zymogen that is proteolytically processed into a two-subunit (p20/p11) active enzyme (PMID:7983002). Its crystal structure bound to a tetrapeptide-aldehyde inhibitor revealed an S4 subsite distinct from ICE, accounting for its preference for DEVD-like cleavage sites (PMID:8673606), a specificity that mirrors C. elegans CED-3 and marks CASP3 as the mammalian functional equivalent of that death protease (PMID:8654923). CASP3 is activated by limited proteolysis at the junction between its large and small subunits, either by cytotoxic-lymphocyte granzyme B followed by autocatalytic prodomain removal (PMID:7566124, PMID:8700869, PMID:8665848, PMID:8702964) or by upstream ICE/CED3-family proteases, placing it downstream in a sequential caspase cascade during Fas-induced death (PMID:8614469, PMID:8662833). Once active, CASP3 cleaves a defined substrate set at DEVD-like sites to dismantle the cell: PARP (PMID:7774019), the DNA-PKcs catalytic subunit (PMID:8642305, PMID:8804412, PMID:8798786), DNA replication factor DSEB/RF-C140 (PMID:9235961), U1-70K snRNP (PMID:8642305), SREBP-1/2 (PMID:8605870), huntingtin (PMID:8696339), the Rho-GTPase regulator D4-GDI (PMID:8626669), actin (PMID:9070648), and the kinase Pak2 (PMID:9786869); it also amplifies the cascade by processing and activating pro-caspase-9 (Mch6) and the lamin-cleaving caspase-6 (Mch2alpha) (PMID:8900201). CASP3 is itself held in check upstream by Bcl-2, which blocks zymogen maturation without physically binding the enzyme (PMID:8663439, PMID:8619857). Genetic ablation establishes that CASP3 is essential for morphogenetic neuronal apoptosis in the developing brain (PMID:8934524, PMID:9512515) and for chromatin condensation and DNA fragmentation, although membrane blebbing, JNK/p38 activation and cell death itself can proceed independently of CASP3 activity in a stimulus- and tissue-specific manner (PMID:9512515, PMID:9362518).

Mechanistic history

Synthesis pass · year-by-year structured walk · 15 steps
  1. 1994 High

    Established the molecular identity of CASP3 as a 32-kDa cysteine protease whose proteolytic processing into two subunits is required for pro-apoptotic activity.

    Evidence Cloning and Sf9 overexpression with reconstitution from recombinant p20/p11 subunits

    PMID:7983002

    Open questions at the time
    • Did not identify the physiological protease(s) that perform the activating cleavage
    • No substrate repertoire defined at this stage
  2. 1995 High

    Defined the first executioner function by showing CASP3 cleaves PARP to its apoptotic signature fragment, linking the protease to a specific nuclear substrate.

    Evidence In vitro protease assay with purified enzyme; CrmA wild-type vs. inactive mutant controls; cell-based PARP cleavage

    PMID:7774019

    Open questions at the time
    • Did not establish whether PARP cleavage is causal for death or a bystander event
    • Upstream activator still unknown
  3. 1995 High

    Identified granzyme B as a physiological activator, connecting CTL-mediated killing to the CASP3/PARP pathway.

    Evidence In vitro cleavage of CPP32 precursor by granzyme B with PARP cleavage readout; independently replicated

    PMID:7566124 PMID:8665848 PMID:8700869 PMID:8702964

    Open questions at the time
    • Granzyme-independent activation routes not yet defined here
  4. 1996 High

    Resolved the activation mechanism and its specificity: granzyme B cleaves between large and small subunits followed by autocatalytic prodomain removal, and does not activate ICE.

    Evidence Cell-free reconstitution, purified-protein cleavage, inhibitor dissection (CPP32 vs. ICE inhibitors), CrmA; KO granzyme B cells confirm non-redundancy

    PMID:8665848 PMID:8700869 PMID:8702964

    Open questions at the time
    • Structural basis of subunit-junction recognition by granzyme B not defined
    • Relative contribution of autocatalysis vs. trans-cleavage in cells unquantified
  5. 1996 High

    Provided the structural explanation for DEVD specificity, distinguishing CED-3-like from ICE-like proteases.

    Evidence X-ray crystallography of inhibitor-bound CPP32/apopain; comparative analysis of the S4 subsite

    PMID:8673606

    Open questions at the time
    • No structure of the apo or fully zymogenic form
    • Does not capture substrate-induced conformational changes
  6. 1996 High

    Placed CASP3 within a sequential protease cascade downstream of ICE-like enzymes and showed it both receives and propagates activation.

    Evidence Cell-free Fas system, ICE-null thymocyte reconstitution with recombinant CASP3, purified upstream activating protease (CAP/Mch2alpha homolog); CASP3 activation of pro-caspase-9 and caspase-6

    PMID:8614469 PMID:8662833 PMID:8900201

    Open questions at the time
    • The full set of physiological upstream initiators was not enumerated
    • Quantitative hierarchy of cascade branches in vivo unresolved
  7. 1996 High

    Mapped a broad DEVD-site substrate repertoire, explaining how CASP3 dismantles nuclear, replication, cytoskeletal, and signaling machinery.

    Evidence In vitro cleavage of DNA-PKcs, U1-70K, SREBP-1/2, huntingtin, D4-GDI, actin (with neoepitope antibodies, N-terminal sequencing, cleavage-site mutagenesis) plus matched in vivo apoptotic fragments and inhibitor specificity

    PMID:8605870 PMID:8626669 PMID:8642305 PMID:8696339 PMID:8798786 PMID:8804412 PMID:9070648

    Open questions at the time
    • Did not establish which cleavages are necessary vs. dispensable for the death phenotype
    • Order and kinetics of substrate processing in cells not fully ordered
  8. 1996 Medium

    Positioned Bcl-2 as an upstream, indirect inhibitor acting at the CASP3 maturation step rather than by binding the protease.

    Evidence Western blot for zymogen processing under Bcl-2 overexpression; negative co-immunoprecipitation for physical interaction

    PMID:8619857 PMID:8663439

    Open questions at the time
    • Negative Co-IP does not define the actual molecular intermediary blocked by Bcl-2
    • Single-lab for the indirect-mechanism conclusion
  9. 1996 High

    Established CASP3 as the major active executioner caspase across diverse apoptotic stimuli, with cell-line-specific processed species.

    Evidence Active-site affinity labeling across multiple tumor lines and stimuli

    PMID:9171342

    Open questions at the time
    • Functional meaning of distinct processed species between lines not resolved
  10. 1996 High

    Demonstrated in vivo non-redundancy: CASP3 is essential for morphogenetic neuronal apoptosis in the developing brain.

    Evidence Germline knockout mice with histological brain phenotyping; independently replicated

    PMID:8934524 PMID:9512515

    Open questions at the time
    • Tissue-specific substrate dependencies underlying the brain phenotype not dissected
  11. 1998 High

    Delimited CASP3's functional scope: required for chromatin condensation and DNA fragmentation but dispensable for other apoptotic hallmarks, in a stimulus- and tissue-specific manner.

    Evidence Comprehensive KO mouse/ES cell/MEF analysis with multiple stimuli; selective DEVD vs. VAD inhibitor epistasis with morphological and kinase readouts

    PMID:9362518 PMID:9512515

    Open questions at the time
    • Identity of the redundant caspases substituting in CASP3-null cells not established here
    • Mechanism of stimulus-specific requirement unresolved
  12. 1999 Medium

    Refined pathway boundaries by showing CASP3-like activity is neither necessary nor sufficient for death in trophic-factor-deprived neurons, where caspase-2 acts independently.

    Evidence Selective inhibitor (DEVD-FMK vs. BAF) and caspase-2 antisense epistasis in PC12 cells and sympathetic neurons

    PMID:9801360

    Open questions at the time
    • Single-lab pharmacological/antisense dissection
    • Does not exclude partial CASP3 contribution masked by redundancy
  13. 2019 Medium

    Added an upstream signaling input by placing CASP3 downstream of an MST1→JNK cascade in diet-associated neuronal apoptosis.

    Evidence shRNA knockdown of MST1 with Western/immunofluorescence in HFD mouse brain and HT22 cells

    PMID:31117242

    Open questions at the time
    • Single-lab correlational signaling pathway
    • Direct vs. indirect link between JNK and CASP3 activation not biochemically resolved
  14. 2020 Medium

    Defined a pharmacological handle on the active-site cysteine, identifying CASP3 Cys-163 as a covalent target for an irreversible small-molecule inhibitor.

    Evidence Alkynyl-modified ursolic acid probe pulldown/proteome ID, molecular docking to Cys-163, biochemical activity assay, in vivo liver injury model

    PMID:33028983

    Open questions at the time
    • Selectivity versus other caspases not fully quantified
    • Single-lab target identification
  15. 2017 Medium

    Identified transcriptional regulation of CASP3 by HOXC13 as a route controlling apoptotic threshold in cancer cells.

    Evidence ChIP showing direct promoter binding; HOXC13 knockdown with CASP3 induction and apoptosis readout in esophageal squamous carcinoma cells

    PMID:29168599

    Open questions at the time
    • Single-lab; generality across tissues unknown
    • Does not link transcriptional control to specific physiological death programs

Open questions

Synthesis pass · forward-looking unresolved questions
  • How CASP3 substrate cleavage choices are prioritized in vivo and which cleavages are causally required for the death phenotype versus tissue-redundant remains unresolved.
  • No systematic mapping of which substrate cleavages are necessary vs. dispensable for death
  • Identity of caspases redundant with CASP3 in null tissues not defined in this corpus
  • Structural basis of zymogen-to-active transition not captured

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0140096 catalytic activity, acting on a protein 11 GO:0016787 hydrolase activity 3
Localization
GO:0005829 cytosol 1
Pathway
R-HSA-5357801 Programmed Cell Death 4 R-HSA-168256 Immune System 3
Partners
BCL2GZMB

Evidence

Reading pass · 33 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
1994 CPP32 (CASP3) encodes a 32-kDa cysteine protease; overexpression in Sf9 insect cells induces apoptosis, and co-expression of recombinant p20 and p11 subunits (derived from the full-length sequence) reconstitutes apoptotic activity, establishing that CPP32 is processed into a two-subunit active complex. Cloning, overexpression in Sf9 cells, co-expression of recombinant subunits The Journal of biological chemistry High 7983002
1995 Purified Yama/CPP32 (CASP3) zymogen, when activated, cleaves PARP to generate the 85-kDa apoptotic fragment; this cleavage is inhibited by CrmA but not by an inactive CrmA point mutant, and CrmA blocks PARP cleavage in apoptotic cells. In vitro protease assay with purified recombinant protein, inhibitor mutagenesis (CrmA point mutant), cell-based PARP cleavage assay Cell High 7774019
1996 The three-dimensional crystal structure of CPP32/apopain complexed with a tetrapeptide-aldehyde inhibitor was determined; the S4 subsite is strikingly different in size and chemical composition from ICE, explaining the distinct substrate specificity of CED-3-related versus ICE-related proteases. X-ray crystallography of inhibitor-bound complex Nature structural biology High 8673606
1995 Granzyme B, secreted by cytotoxic T lymphocytes, cleaves and activates the CPP32 precursor, providing a mechanistic link between CTL-mediated killing and activation of the CPP32/PARP cleavage pathway. In vitro cleavage assay: granzyme B incubated with CPP32 precursor; PARP cleavage as functional readout Nature High 7566124 8665848 8700869 8702964
1996 Granzyme B directly cleaves CPP32 between its large and small subunits, generating an active protease; the prodomain is then removed by an autocatalytic step (two-step mechanism). CrmA inhibits granzyme B-mediated CPP32 processing and apoptosis. Cell-free extract reconstitution, inhibitor studies (tetrapeptide CPP32 inhibitor vs. ICE inhibitor), CrmA co-expression The EMBO journal High 8665848
1996 Granzyme B directly activates purified Yama/CPP32 by limited proteolysis; activated Yama can bind inhibitors and cleave PARP. Processing of ICE by granzyme B does not activate ICE, demonstrating substrate selectivity. In vitro protease assay with purified proteins; PARP cleavage and inhibitor-binding as functional readouts Proceedings of the National Academy of Sciences of the United States of America High 8700869
1996 Granzyme B from granzyme B-deficient mouse cytolytic cells fails to cleave and activate CPP32 and fails to induce DNA fragmentation in target cells, confirming a non-redundant role for granzyme B in CPP32 activation and downstream DNA fragmentation. Granzyme B knockout cells, peptide inhibitor of CPP32-like proteases, 51Cr release assay The Journal of biological chemistry High 8702964
1996 CPP32/apopain cleaves U1-70 kDa snRNP protein and the catalytic subunit of DNA-dependent protein kinase (DNA-PKcs) at DEVD-like sites in vitro and in apoptotic cells, with fragments identical to those seen in intact apoptotic cells; cleavage is abolished by nanomolar Ac-DEVD-CHO. In vitro protease assay with purified apopain and isolated substrates; comparison of in vitro and in vivo cleavage fragments; inhibitor studies The Journal of experimental medicine High 8642305
1996 CPP32 cleaves SREBP-1 and SREBP-2 at an aspartate residue during apoptosis, liberating transcriptionally active N-terminal fragments; an Asp→Ala mutation at the CPP32 cleavage site abolishes apoptosis-induced (but not sterol-regulated) SREBP cleavage. In vitro cleavage assay with purified CPP32; site-directed mutagenesis of the cleavage site; cell-based apoptosis assays (staurosporine, anti-Fas, etoposide) The EMBO journal High 8605870
1996 CPP32 processes pro-Mch6 (caspase-9) and pro-Mch2alpha (caspase-6, the lamin-cleaving enzyme) in vitro, activating them; site-directed mutagenesis identified specific aspartate processing sites. Granzyme B activates CPP32 which then activates Mch2alpha, establishing a protease cascade: granzyme B → CPP32 → Mch2alpha/Mch6. In vitro protease assay with purified recombinant enzymes; site-directed mutagenesis of processing sites; co-incubation with cellular extracts The Journal of biological chemistry High 8900201
1996 CPP32/apopain cleaves actin in vitro to 15- and 31-kDa fragments; a selective CPP32 inhibitor (Z-EVD-CH2-DCB) blocks actin cleavage and apoptosis in VP-16-treated U937 cells, and actin cleavage occurs in vivo during apoptosis. In vitro cleavage assay; antibody against cleavage-site neoepitope; selective caspase-3 inhibitor; cell-based apoptosis assay Oncogene High 9070648
1996 D4-GDI (a GDP dissociation inhibitor for Rho family GTPases) is cleaved by recombinant CPP32 in vitro at DELD19↓S; this cleavage also occurs in Jurkat cells undergoing Fas- or staurosporine-induced apoptosis and is blocked by DEVD-CHO but not by YVAD-CHO. In vitro cleavage assay with recombinant E. coli-expressed CPP32; N-terminal sequencing of cleavage fragment; cell-based inhibitor studies The Journal of biological chemistry High 8626669
1996 CPP32/Yama/apopain cleaves the catalytic subunit (p460) of DNA-PK in vitro, generating 230- and 160-kDa fragments and abolishing DNA-PK activity; cleavage is blocked by a selective CPP32 inhibitor but not by other protease inhibitors. In vitro cleavage assay with purified DNA-PK; kinase activity assay; selective inhibitor studies; cell-based apoptosis model FEBS letters High 8798786 8804412
1996 Huntingtin is cleaved specifically by apopain (CPP32) in apoptotic extracts and by purified apopain; the rate of cleavage increases with polyglutamine tract length. In vitro cleavage assay with purified apopain and recombinant huntingtin variants; apoptotic cell extract cleavage assay Nature genetics High 8696339
1996 Fas-induced apoptosis sequentially activates ICE-like proteases followed by CPP32-like proteases; CPP32 activity accumulates in the cytosol in an ICE-dependent manner, and supplementing cell lysates from ICE-null thymocytes with recombinant CPP32 reconstitutes nuclear apoptosis. Cell-free apoptosis system; specific inhibitors of ICE- vs. CPP32-like proteases; ICE-null mouse thymocytes; recombinant CPP32 reconstitution Nature High 8614469
1996 An ICE-family protease (CAP/Mch2alpha homolog) purified from hamster cells cleaves and activates CPP32 in vitro; CAP activity is inhibited by CrmA and is itself activated by proteolytic cleavage, consistent with a cascade upstream of CPP32. Protein purification, in vitro CPP32 activation assay, protein sequencing, inhibitor studies The Journal of biological chemistry High 8662833
1996 CPP32 proenzyme is proteolytically processed and activated in Fas-ligated Jurkat cells; CPP32 activation is blocked by cell-permeable inhibitors of aspartate-directed cysteine proteases and by overexpression of Bcl-2, placing Bcl-2 at or upstream of the CPP32 activation step. Western blot for CPP32 processing, cell-permeable inhibitors, Bcl-2 overexpression, cell viability assays The Journal of biological chemistry High 8663439
1996 Bcl-2 overexpression prevents CPP32 maturation (zymogen cleavage) and PARP cleavage in TNFα-induced apoptosis of U937 monocytes; no physical interaction between Bcl-2 and CPP32 was detected, indicating the inhibitory effect is indirect. Western blot for CPP32 processing; PARP cleavage assay; co-immunoprecipitation (negative result for physical interaction); Bcl-2 overexpression Biochemical and biophysical research communications Medium 8619857
1996 CPP32-like protease activity is activated in Fas-induced apoptosis of Jurkat T cells; the activity has kinetics similar to purified apopain, cleaves PARP, is recognized by anti-CPP32 antibodies but not anti-ICE antibodies, and a selective apopain inhibitor prevents Fas-induced apoptosis. Biochemical isolation of protease from apoptotic cells; kinetic analysis; substrate cleavage; antibody recognition; selective inhibitor The Journal of biological chemistry High 8567626
1996 CPP32 (caspase-3) cleaves p21-activated kinase gamma-PAK (Pak2) in vitro into two fragments (residues 1-212 and 213-524); subsequent autophosphorylation of both cleavage products occurs, and activation of the catalytic domain requires autophosphorylation at Thr-402 (mutation Thr402Ala abolishes activity). In vitro CPP32 cleavage assay with recombinant gamma-PAK; autophosphorylation assay; site-directed mutagenesis (Thr402Ala) The Journal of biological chemistry High 9786869
1997 The large subunit of DNA replication factor DSEB/RF-C140 is cleaved by caspase-3 at DEVD706/G during Fas-induced apoptosis in Jurkat cells; Asp706→Ala mutation abolishes cleavage in vitro; cleavage is inhibited by Ac-DEVD-CHO and iodoacetamide but not by CrmA or Ac-YVAD-CHO; recombinant caspase-3 (but not caspase-1) reproduces the in vivo cleavage. In vitro translated substrate cleavage assay; site-directed mutagenesis of cleavage site; selective caspase inhibitors; recombinant caspase-3 reconstitution The Journal of biological chemistry High 9235961
1996 CPP32-deficient (knockout) mice display profoundly defective neuronal apoptosis during brain development, including absence of pyknotic clusters at morphogenetic sites and hyperplasias, establishing that CPP32 is essential for morphogenetic cell death in the mammalian brain in vivo. Homologous recombination knockout; histological analysis; embryonic brain phenotyping Nature High 8934524 9512515
1998 CPP32 (caspase-3) is required for chromatin condensation and DNA degradation in certain apoptotic cell types, but other hallmarks of apoptosis can proceed in its absence; the requirement is stimulus- and tissue-specific (e.g., required for UV- but not γ-irradiation-induced apoptosis in ES cells; required for TNFα-induced apoptosis in transformed MEFs but not thymocytes). Comprehensive analysis of CPP32-deficient mice, ES cells, and MEFs with multiple apoptotic stimuli; DNA fragmentation, chromatin condensation assays Genes & development High 9512515
1996 C. elegans CED-3 cysteine protease has substrate specificity similar to CPP32 (both prefer DEVD-like sites), distinct from ICE or NEDD2/ICH-1, supporting CPP32 as the mammalian functional equivalent of CED-3. Purification of CED-3 and four ICE-family proteases; direct comparative substrate specificity assays Genes & development High 8654923
1997 Active CPP32 (caspase-3) is the major active caspase in apoptotic tumor cells across multiple stimuli and cell lines; CPP32 is present as multiple active species whose pattern varies between cell lines but is constant across stimuli within a given line, indicating cell-line-specific processing differences. Novel active-caspase detection approach (affinity labeling); multiple tumor cell lines and apoptotic stimuli; CPP32 and Mch2 identified simultaneously The EMBO journal High 9171342
1997 CPP32 activation during Fas-induced apoptosis requires macromolecular synthesis and upstream CED3/ICE protease activity; affinity labeling of the active-site cysteine identified p20/p18 processed subunits in apoptotic but not necrotic granule neurons, with CPP32 activation preceding PARP cleavage and DNA laddering. Active-site affinity labeling; RNA and protein synthesis inhibitors; CED3/ICE inhibitor pretreatment; temporal Western blot analysis The Journal of neuroscience Medium 8987778
1997 Fas-induced activation of JNK/SAPK (via MKK7) and p38 (via MKK6), cell shrinkage, surface blebbing, Apo2.7 antigen induction, and cell death all occur independently of CPP32-like protease activity; CPP32-like proteases are specifically required for chromatin condensation and DNA fragmentation but not for other Fas-induced apoptotic events. Selective caspase inhibitors (DEVD-type vs. VAD-type) in Jurkat and KB cells; kinase activation assays; morphological and cell death assessments The Journal of cell biology High 9362518
1998 During T-cell negative selection in vivo, CPP32 activation (detected by proteolytic cleavage of p32 zymogen) occurs specifically upon anti-CD3 crosslinking or antigen challenge (pigeon cytochrome C in MHC-compatible mice) and precedes phosphatidylserine exposure; it is not detected during spontaneous thymocyte apoptosis, suggesting a distinct pathway for activation-induced cell death. Western blot for CPP32 processing; PARP cleavage; in vivo antigen challenge of TCR-transgenic mice; caspase inhibitor (zVAD) studies The Journal of experimental medicine Medium 9348308
1997 Thyroid hormone up-regulates Xenopus CPP32/apopain/Yama gene expression in a tadpole tail myoblast cell line (XLT-15), and a CPP32/apopain inhibitor (Ac-DEVD-CHO) prevents thyroid hormone-induced apoptosis, while an ICE inhibitor does not, establishing that CPP32 mediates thyroid hormone-dependent apoptosis in this model. RT-PCR for CPP32 mRNA; TUNEL assay; selective inhibitor (DEVD-CHO vs. YVAD-CHO); cell viability The Journal of biological chemistry Medium 9030578
1998 MST1 kinase activates JNK which in turn activates caspase-3 (Casp3) in a signaling cascade mediating neuronal apoptosis in high-fat diet mouse brain and HT22 cells; shRNA knockdown of MST1 significantly reduces JNK/Casp3 signaling. Western blot; immunofluorescence; shRNA knockdown of MST1; in vivo HFD mouse model International journal of molecular sciences Medium 31117242
1999 Caspase-2 (Nedd-2) processing and cell death in trophic factor-deprived PC12 cells and sympathetic neurons occur independently of caspase-3 (CPP32)-like activity; DEVD-FMK inhibits caspase-3-like activity but does not suppress caspase-2 processing or cell death; caspase-3-like activity is neither necessary nor sufficient for death in this paradigm. Selective caspase inhibitors (DEVD-FMK vs. BAF/zVAD-FMK); caspase-2 antisense oligonucleotide; Western blot for caspase-2 processing; cell survival assays The Journal of neuroscience Medium 9801360
2020 Ursolic acid (UA) metabolite irreversibly inhibits CASP3 by forming a covalent bond with Cys-163 of caspase-3 via an epoxy group; an alkynyl-modified UA probe captured CASP3 as the primary target from mouse liver, and binding was verified by molecular docking, biochemical evaluation in HepG2 cells, and in vivo liver injury attenuation. Chemical probe (alkynyl-modified UA) pulldown/proteome identification; molecular docking to active-site Cys-163; biochemical CASP3 activity assay; in vivo alcoholic liver disease model Acta pharmacologica Sinica Medium 33028983
2017 HOXC13 represses transcription of CASP3 by directly binding to the CASP3 promoter region (ChIP analysis); knockdown of HOXC13 in esophageal squamous cell carcinoma cells upregulates CASP3 and induces apoptosis. ChIP analysis; HOXC13 knockdown; RT-PCR and Western blot for CASP3; apoptosis assay Cancer science Medium 29168599

Source papers

Stage 0 corpus · 100 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
1995 Yama/CPP32 beta, a mammalian homolog of CED-3, is a CrmA-inhibitable protease that cleaves the death substrate poly(ADP-ribose) polymerase. Cell 2332 7774019
1996 Decreased apoptosis in the brain and premature lethality in CPP32-deficient mice. Nature 1635 8934524
1994 CPP32, a novel human apoptotic protein with homology to Caenorhabditis elegans cell death protein Ced-3 and mammalian interleukin-1 beta-converting enzyme. The Journal of biological chemistry 1084 7983002
1996 Sequential activation of ICE-like and CPP32-like proteases during Fas-mediated apoptosis. Nature 939 8614469
1998 Essential contribution of caspase 3/CPP32 to apoptosis and its associated nuclear changes. Genes & development 740 9512515
1995 Activation of the apoptotic protease CPP32 by cytotoxic T-cell-derived granzyme B. Nature 635 7566124
1996 Apopain/CPP32 cleaves proteins that are essential for cellular repair: a fundamental principle of apoptotic death. The Journal of experimental medicine 549 8642305
1997 Activation of CPP32-like caspases contributes to neuronal apoptosis and neurological dysfunction after traumatic brain injury. The Journal of neuroscience : the official journal of the Society for Neuroscience 497 9295387
1996 Cleavage of huntingtin by apopain, a proapoptotic cysteine protease, is modulated by the polyglutamine tract. Nature genetics 482 8696339
1996 CPP32/apopain is a key interleukin 1 beta converting enzyme-like protease involved in Fas-mediated apoptosis. The Journal of biological chemistry 471 8567626
1997 Immunohistochemical analysis of in vivo patterns of expression of CPP32 (Caspase-3), a cell death protease. Cancer research 393 9108467
1996 The three-dimensional structure of apopain/CPP32, a key mediator of apoptosis. Nature structural biology 366 8673606
1997 Multiple species of CPP32 and Mch2 are the major active caspases present in apoptotic cells. The EMBO journal 328 9171342
1996 Fas-induced activation of the cell death-related protease CPP32 Is inhibited by Bcl-2 and by ICE family protease inhibitors. The Journal of biological chemistry 305 8663439
1996 The Caenorhabditis elegans cell-death protein CED-3 is a cysteine protease with substrate specificities similar to those of the human CPP32 protease. Genes & development 287 8654923
1996 Cleavage of sterol regulatory element binding proteins (SREBPs) by CPP32 during apoptosis. The EMBO journal 283 8605870
1996 The Ced-3/interleukin 1beta converting enzyme-like homolog Mch6 and the lamin-cleaving enzyme Mch2alpha are substrates for the apoptotic mediator CPP32. The Journal of biological chemistry 269 8900201
1998 Activation of caspase 3 (CPP32)-like proteases is essential for TNF-alpha-induced hepatic parenchymal cell apoptosis and neutrophil-mediated necrosis in a murine endotoxin shock model. Journal of immunology (Baltimore, Md. : 1950) 262 9531309
1997 Activation of the CED3/ICE-related protease CPP32 in cerebellar granule neurons undergoing apoptosis but not necrosis. The Journal of neuroscience : the official journal of the Society for Neuroscience 259 8987778
1996 The cytotoxic cell protease granzyme B initiates apoptosis in a cell-free system by proteolytic processing and activation of the ICE/CED-3 family protease, CPP32, via a novel two-step mechanism. The EMBO journal 251 8665848
1999 Processing and analysis of CASP3 protein structure predictions. Proteins 220 10526349
1997 Actin cleavage by CPP-32/apopain during the development of apoptosis. Oncogene 220 9070648
1996 D4-GDI, a substrate of CPP32, is proteolyzed during Fas-induced apoptosis. The Journal of biological chemistry 206 8626669
1996 Identification and characterization of CPP32/Mch2 homolog 1, a novel cysteine protease similar to CPP32. The Journal of biological chemistry 188 8567622
1996 Involvement of CPP32/Yama(-like) proteases in Fas-mediated apoptosis. Cancer research 171 8620480
1996 Proteolytic activation of the cell death protease Yama/CPP32 by granzyme B. Proceedings of the National Academy of Sciences of the United States of America 167 8700869
1996 Activation of the CPP32 protease in apoptosis induced by 1-beta-D-arabinofuranosylcytosine and other DNA-damaging agents. Blood 166 8822910
1996 Activation of the CPP32 apoptotic protease by distinct signaling pathways with differential sensitivity to Bcl-xL. The Journal of biological chemistry 152 8663611
1996 Overexpression of Bcl-2 or Bcl-xL inhibits Ara-C-induced CPP32/Yama protease activity and apoptosis of human acute myelogenous leukemia HL-60 cells. Cancer research 152 8840993
1996 Bcl-2 and adenovirus E1B 19 kDA protein prevent E1A-induced processing of CPP32 and cleavage of poly(ADP-ribose) polymerase. Oncogene 144 8637709
1996 Induction of CPP32-like activity in PC12 cells by withdrawal of trophic support. Dissociation from apoptosis. The Journal of biological chemistry 143 8940042
1997 Activation of CPP32 during apoptosis of neurons and astrocytes. Journal of neuroscience research 141 9130145
1997 The roles of Bcl-X(L) and apopain in the control of erythropoiesis by erythropoietin. Blood 136 9226163
1997 Fas induces cytoplasmic apoptotic responses and activation of the MKK7-JNK/SAPK and MKK6-p38 pathways independent of CPP32-like proteases. The Journal of cell biology 136 9362518
1996 Cleavage of CPP32 by granzyme B represents a critical role for granzyme B in the induction of target cell DNA fragmentation. The Journal of biological chemistry 128 8702964
2010 Common variants in CASP3 confer susceptibility to Kawasaki disease. Human molecular genetics 124 20423928
1999 Alteration of caspase-3 (CPP32/Yama/apopain) in wild-type MCF-7, breast cancer cells. Oncology reports 120 9864397
1996 DNA-dependent protein kinase is a target for a CPP32-like apoptotic protease. The Journal of biological chemistry 119 8798786
1997 High levels of expression and nuclear localization of interleukin-1 beta converting enzyme (ICE) and CPP32 in favorable human neuroblastomas. Cancer research 116 9377572
1998 Cleavage and activation of p21-activated protein kinase gamma-PAK by CPP32 (caspase 3). Effects of autophosphorylation on activity. The Journal of biological chemistry 112 9786869
1998 Caspase-2 (Nedd-2) processing and death of trophic factor-deprived PC12 cells and sympathetic neurons occur independently of caspase-3 (CPP32)-like activity. The Journal of neuroscience : the official journal of the Society for Neuroscience 95 9801360
1997 Characterization of CPP32-like protease activity following apoptotic challenge in SH-SY5Y neuroblastoma cells. Journal of neurochemistry 94 9166725
2011 ITPKC and CASP3 polymorphisms and risks for IVIG unresponsiveness and coronary artery lesion formation in Kawasaki disease. The pharmacogenomics journal 92 21987091
2004 Somatic mutations of CASP3 gene in human cancers. Human genetics 92 15127291
1997 Induction of apoptosis and CPP32 expression by thyroid hormone in a myoblastic cell line derived from tadpole tail. The Journal of biological chemistry 91 9030578
1999 Overexpression of protein kinase C isoforms protects RAW 264.7 macrophages from nitric oxide-induced apoptosis: involvement of c-Jun N-terminal kinase/stress-activated protein kinase, p38 kinase, and CPP-32 protease pathways. Journal of immunology (Baltimore, Md. : 1950) 86 10092794
1999 Activation of c-Jun NH2-terminal kinase and subsequent CPP32/Yama during topoisomerase inhibitor beta-lapachone-induced apoptosis through an oxidation-dependent pathway. Cancer research 86 9927052
1997 Immunolocalization of the ICE/Ced-3-family protease, CPP32 (Caspase-3), in non-Hodgkin's lymphomas, chronic lymphocytic leukemias, and reactive lymph nodes. Blood 86 9160689
1996 Purification and characterization of an interleukin-1beta-converting enzyme family protease that activates cysteine protease P32 (CPP32). The Journal of biological chemistry 86 8662833
1996 Bcl-xL overexpression inhibits taxol-induced Yama protease activity and apoptosis. Cell growth & differentiation : the molecular biology journal of the American Association for Cancer Research 84 8853905
1999 Progress in protein structure prediction: assessment of CASP3. Current opinion in structural biology 80 10361096
1997 Processing/activation of CPP32-like proteases is involved in transforming growth factor beta1-induced apoptosis in rat hepatocytes. Hepatology (Baltimore, Md.) 78 9185777
2014 MiR-378 overexpression attenuates high glucose-suppressed osteogenic differentiation through targeting CASP3 and activating PI3K/Akt signaling pathway. International journal of clinical and experimental pathology 73 25400823
1998 Immunohistochemistry of Caspase3/CPP32 in human stomach and its correlation with cell proliferation and apoptosis. Anticancer research 73 9891491
1997 Intact cell evidence for the early synthesis, and subsequent late apopain-mediated suppression, of poly(ADP-ribose) during apoptosis. Experimental cell research 72 9168807
1997 Specific activation of the cysteine protease CPP32 during the negative selection of T cells in the thymus. The Journal of experimental medicine 71 9348308
1999 Characterization of the interleukin-1beta-converting enzyme/ced-3-family protease, caspase-3/CPP32, in Hodgkin's disease: lack of caspase-3 expression in nodular lymphocyte predominance Hodgkin's disease. The American journal of pathology 70 10329597
1998 Crucial role of apopain in the peroxynitrite-induced apoptotic DNA fragmentation. Free radical biology & medicine 69 9870561
1997 The apoptotic cysteine protease CPP32. The international journal of biochemistry & cell biology 67 9202418
2010 CASP3 gene single-nucleotide polymorphism (rs72689236) and Kawasaki disease in Taiwanese children. Journal of human genetics 66 21160486
1999 Postnatal distribution of cpp32/caspase 3 mRNA in the mouse central nervous system: an in situ hybridization study. The Journal of comparative neurology 66 10379822
1996 Bcl-2 overexpression blocks activation of the death protease CPP32/Yama/apopain. Biochemical and biophysical research communications 66 8619857
1996 Ligation of CD40 rescues Ramos-Burkitt lymphoma B cells from calcium ionophore- and antigen receptor-triggered apoptosis by inhibiting activation of the cysteine protease CPP32/Yama and cleavage of its substrate PARP. FEBS letters 65 8647264
1998 Involvement of CPP32/Caspase-3 in c-Myc-induced apoptosis. Oncogene 58 9467964
2016 Dioscin suppresses hepatocellular carcinoma tumor growth by inducing apoptosis and regulation of TP53, BAX, BCL2 and cleaved CASP3. Phytomedicine : international journal of phytotherapy and phytopharmacology 51 27765352
2000 Reduced expression of ICE/caspase1 and CPP32/caspase3 in human hepatocellular carcinoma. Anticancer research 51 10928128
1999 Modulation of nitric oxide-induced apoptotic death of HL-60 cells by protein kinase C and protein kinase A through mitogen-activated protein kinases and CPP32-like protease pathways. Cellular immunology 51 10357879
1998 Resistance to apoptosis correlates with a highly proliferative phenotype and loss of Fas and CPP32 (caspase-3) expression in human leukemia cells. International journal of cancer 51 9455811
2015 Increased expression and colocalization of GAP43 and CASP3 after brain ischemic lesion in mouse. Neuroscience letters 50 25929184
1997 Apoptotic cell death and caspase 3 (CPP32) activation induced by calcium ionophore at low concentrations and their prevention by nerve growth factor in PC12 cells. European journal of biochemistry 44 9363747
2008 CASP3 polymorphisms and risk of squamous cell carcinoma of the head and neck. Clinical cancer research : an official journal of the American Association for Cancer Research 43 18829519
1996 Molecular characterization of mouse and rat CPP32 beta gene encoding a cysteine protease resembling interleukin-1 beta converting enzyme and CED-3. Oncogene 43 8761296
1998 Apoptosis of undifferentiated progenitors and granule cell precursors in the postnatal human cerebellar cortex correlates with expression of BCL-2, ICE, and CPP32 proteins. The Journal of comparative neurology 41 9733083
1998 Wortmannin enhances activation of CPP32 (Caspase-3) induced by TNF or anti-Fas. Cell death and differentiation 38 10200474
1998 Conformationally constrained inhibitors of caspase-1 (interleukin-1 beta converting enzyme) and of the human CED-3 homologue caspase-3 (CPP32, apopain). Bioorganic & medicinal chemistry letters 38 9873617
1996 CPP32/Yama/apopain cleaves the catalytic component of DNA-dependent protein kinase in the holoenzyme. FEBS letters 38 8804412
2020 Ursolic acid reduces hepatocellular apoptosis and alleviates alcohol-induced liver injury via irreversible inhibition of CASP3 in vivo. Acta pharmacologica Sinica 37 33028983
2019 MST1 Regulates Neuronal Cell Death via JNK/Casp3 Signaling Pathway in HFD Mouse Brain and HT22 Cells. International journal of molecular sciences 37 31117242
2013 A replication study for association of ITPKC and CASP3 two-locus analysis in IVIG unresponsiveness and coronary artery lesion in Kawasaki disease. PloS one 36 23894522
1997 Bcl-2 prevents activation of CPP32 cysteine protease and cleavage of poly (ADP-ribose) polymerase and U1-70 kD proteins in staurosporine-mediated apoptosis. Cell death and differentiation 36 16465208
1997 Identification and mapping of Casp7, a cysteine protease resembling CPP32 beta, interleukin-1 beta converting enzyme, and CED-3. Genomics 35 9070923
1997 Interleukin-1beta-converting enzyme and CPP32 are involved in ultraviolet B-induced apoptosis of SV40-transformed human keratinocytes. Biochemical and biophysical research communications 34 9223451
1997 The large subunit of the DNA replication complex C (DSEB/RF-C140) cleaved and inactivated by caspase-3 (CPP32/YAMA) during Fas-induced apoptosis. The Journal of biological chemistry 34 9235961
2022 A Systematic Pan-Cancer Analysis of CASP3 as a Potential Target for Immunotherapy. Frontiers in molecular biosciences 32 35573727
2012 A functional variant at the miR-885-5p binding site of CASP3 confers risk of both index and second primary malignancies in patients with head and neck cancer. FASEB journal : official publication of the Federation of American Societies for Experimental Biology 32 23271051
1997 Specific expression of CPP32 in sensory neurons of mouse embryos and activation of CPP32 in the apoptosis induced by a withdrawal of NGF. Biochemical and biophysical research communications 32 9070890
1999 Inhibition of transforming growth factor beta1-induced hepatoma cell apoptosis by liver tumor promoters: characterization of primary signaling events and effects on CPP32-like caspase activity. Cell death and differentiation 31 10200566
1998 Vinorelbine induces apoptosis and caspase-3 (CPP32) expression in leukemia and lymphoma cells: a comparison with vincristine. Leukemia & lymphoma 30 9720729
1997 Immunohistochemical analysis of interleukin-1beta-converting enzyme/Ced-3 family protease, CPP32/Yama/Caspase-3, in Hodgkin's disease. Blood 30 9310497
1998 Apoptotic cell death and CPP32-like activation induced by thapsigargin and their prevention by nerve growth factor in PC12 cells. Biochimica et biophysica acta 29 9459486
2020 Dihydroartemisinin inhibits the tumorigenesis and invasion of gastric cancer by regulating STAT1/KDR/MMP9 and P53/BCL2L1/CASP3/7 pathways. Pathology, research and practice 27 33370709
2017 HOXC13 promotes proliferation of esophageal squamous cell carcinoma via repressing transcription of CASP3. Cancer science 27 29168599
2016 Oncogenic miR-137 contributes to cisplatin resistance via repressing CASP3 in lung adenocarcinoma. American journal of cancer research 27 27429846
2000 Regulation of apoptosis reduction in the cisplatin-resistant A431 cell line by Bcl-2 and CPP32. Chemotherapy 27 10601800
1996 Interleukin-7 inhibits apoptosis of mouse malignant T-lymphoma cells by both suppressing the CPP32-like protease activation and inducing the Bcl-2 expression. Oncogene 26 8950980
2000 Enhancement of chemotherapeutic agents induced-apoptosis associated with activation of c-Jun N-terminal kinase 1 and caspase 3 (CPP32) in bax-transfected gastric cancer cells. Anticancer research 25 10769693
2000 The pattern of CPP32/caspase-3 expression reflects the biological behavior of the human pancreatic duct cell tumors. Pancreas 25 11075989
2005 Insulin-like growth factor-I decreased etoposide-induced apoptosis in glioma cells by increasing bcl-2 expression and decreasing CPP32 activity. Neurological research 24 15829155
2000 Expression and activation of caspase-3/CPP32 in CD34(+) cord blood cells is linked to apoptosis after growth factor withdrawal. Experimental hematology 23 10989191
1999 Specific dual effect of cycloheximide on B lymphocyte apoptosis: involvement of CPP32/caspase-3. Biochemical pharmacology 22 10403522

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