Affinage

CASP2

Caspase-2 · UniProt P42575

Round 2 corrected
Length
452 aa
Mass
50.7 kDa
Annotated
2026-04-28
73 papers in source corpus 26 papers cited in narrative 26 extracted findings

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

Caspase-2 is an initiator cysteine protease that couples diverse cellular stresses—including genotoxic damage, trophic factor withdrawal, and sustained ER stress—to the mitochondrial apoptotic pathway. It is synthesized as an inactive zymogen whose CARD-containing prodomain directs nuclear and Golgi localization, and is activated by CARD–CARD-mediated recruitment into the PIDDosome complex (PIDD–RAIDD–CASP2), where proximity-induced dimerization precedes autoprocessing (PMID:15073321, PMID:9695946, PMID:9506977). Once active, caspase-2 acts upstream of mitochondria to cleave Bid and directly permeabilize the outer mitochondrial membrane, releasing cytochrome c, AIF, and Smac to engage the caspase-9/caspase-3 amplification cascade; it also cleaves golgin-160 to promote Golgi disassembly during apoptosis (PMID:11832478, PMID:10791974, PMID:12193789). Beyond apoptosis, CASP2 functions as an endogenous repressor of autophagy through the AMPK–mTOR and AMPK–MAPK axes (PMID:24879153), and biallelic loss-of-function variants in CASP2 cause a neurodevelopmental lissencephaly–pachygyria syndrome linked to PIDDosome dysfunction (PMID:37880421).

Mechanistic history

Synthesis pass · year-by-year structured walk · 10 steps
  1. 1994 High

    The initial identification of CASP2 (ICH-1/Nedd2) established it as a caspase family member capable of promoting apoptosis, with an alternatively spliced short isoform acting as a dominant-negative suppressor—resolving the question of whether a second mammalian ICE homolog participates in cell death.

    Evidence Overexpression of long and short isoforms in mammalian cells with serum deprivation and BCL-2 epistasis assays

    PMID:7958843 PMID:8087842

    Open questions at the time
    • Endogenous substrates unknown
    • Mechanism of activation not addressed
    • Relationship to mitochondrial pathway uncharacterized
  2. 1997 High

    Discovery of the RAIDD/CRADD adaptor answered how CASP2 is recruited to upstream death signaling: RAIDD bridges CASP2 (via CARD–CARD interaction) and RIP (via death domain), establishing the first model for a CASP2 activation platform.

    Evidence Yeast two-hybrid, reciprocal co-immunoprecipitation, and domain deletion mapping

    PMID:8985253 PMID:9044836

    Open questions at the time
    • Identity of the upstream trigger that engages RAIDD was unknown
    • Stoichiometry and structure of activation complex unresolved
    • Whether RAIDD is required in vivo not tested
  3. 1998 High

    Structural and cell-biological studies resolved two key mechanistic questions: (1) the NMR structure of the RAIDD CARD revealed complementary charged surfaces mediating CARD–CARD interaction with CASP2, and (2) the CASP2 prodomain was shown to direct nuclear localization and to promote zymogen dimerization prior to autoprocessing.

    Evidence NMR structure with mutagenesis; GFP-prodomain fusions and subcellular fractionation; yeast dimerization assay with processing-deficient mutants

    PMID:9506977 PMID:9695946 PMID:9733748

    Open questions at the time
    • Nuclear function of caspase-2 versus cytoplasmic function not distinguished
    • Structure of full-length CASP2 or its complex with RAIDD not solved
    • Signal connecting nuclear CASP2 to mitochondrial permeabilization unknown
  4. 2000 High

    Identification of golgin-160 as a Golgi-localized caspase-2-specific substrate revealed a non-nuclear function and explained how CASP2 contributes to Golgi fragmentation during apoptosis.

    Evidence Subcellular fractionation, immunofluorescence, in vitro cleavage assays, and cleavage-site mutagenesis

    PMID:10791974

    Open questions at the time
    • Whether Golgi cleavage is required for cell death or is a bystander event
    • Full substrate repertoire at the Golgi not mapped
  5. 2002 High

    Three convergent studies placed CASP2 unambiguously upstream of mitochondria: active caspase-2 directly permeabilizes isolated mitochondria (releasing cytochrome c, AIF, Smac) and cleaves Bid, while pharmacological or genetic inhibition of CASP2 blocks cytochrome c release and downstream caspase-9/caspase-3 activation.

    Evidence Purified recombinant caspase-2 on isolated mitochondria; z-VDVAD-fmk and antisense; cell-free reconstitution; Bcl-2/Bcl-xL epistasis

    PMID:11832478 PMID:12065594 PMID:12193789

    Open questions at the time
    • Whether CASP2 directly forms pores in mitochondrial membranes or requires Bax/Bak was unresolved
    • Relative contributions of Bid cleavage versus direct permeabilization unclear
  6. 2004 High

    Identification of the PIDDosome (PIDD–RAIDD–CASP2) as the physiological activation platform for caspase-2 answered how genotoxic stress triggers CASP2 activation: the p53-inducible protein PIDD scaffolds complex assembly.

    Evidence Native complex immunoprecipitation; PIDD overexpression and knockdown; caspase-2 activity assays under genotoxic stress

    PMID:15073321

    Open questions at the time
    • Whether the PIDDosome is the sole activation mechanism for CASP2 or context-dependent
    • Structural basis of the tripartite complex unknown at the time
  7. 2005 High

    The finding that PIDD forms a separate PIDD–RIP1–NEMO complex that activates NF-κB independently of caspase-2 showed that the PIDDosome is a bifunctional signaling hub, and CASP2 is required only for its apoptotic output.

    Evidence RNAi of PIDD, RIP1, and CASP2; NF-κB reporter assays; NEMO modification analysis

    PMID:16360037

    Open questions at the time
    • How the cell chooses between apoptotic and NF-κB-activating PIDDosome assemblies is unknown
    • Post-translational signals governing complex switching not identified
  8. 2012 High

    The discovery that IRE1α RNase degrades miRNA precursors (miR-17, -34a, -96, -125b) that repress CASP2 translation during ER stress answered how CASP2 protein levels are acutely upregulated to commit cells to apoptosis under prolonged UPR signaling.

    Evidence Cell-free IRE1α cleavage of miRNA precursors; ribosome profiling; CASP2 protein quantification; miRNA mimic/inhibitor epistasis

    PMID:23042294

    Open questions at the time
    • Whether additional post-transcriptional regulators cooperate with IRE1α-mediated derepression
    • Quantitative threshold of CASP2 protein needed for apoptosis commitment not defined
  9. 2014 High

    Genetic knockout and rescue experiments established an unexpected non-apoptotic role for CASP2 as an endogenous suppressor of autophagy via AMPK–mTOR and AMPK–MAPK pathways, expanding its function beyond cell death.

    Evidence Casp2 KO MEFs with re-expression rescue; LC3/p62 autophagy flux assays; AMPK/mTOR pathway inhibitors; ROS measurement

    PMID:24879153

    Open questions at the time
    • Whether CASP2 directly cleaves an AMPK pathway component or acts indirectly through ROS
    • In vivo physiological contexts in which CASP2-regulated autophagy is relevant remain unclear
  10. 2023 Medium

    Human genetic evidence linked biallelic CASP2 loss-of-function to a neurodevelopmental lissencephaly–pachygyria syndrome, establishing CASP2 as essential for cortical development and phenocopying CRADD and PIDD1 deficiency.

    Evidence Exome sequencing of 7 patients from 5 families; RNA splicing validation of a splice-site variant; neuroimaging

    PMID:37880421

    Open questions at the time
    • No in vitro functional reconstitution of the truncating variants
    • Mechanism by which PIDDosome dysfunction causes lissencephaly (apoptotic vs. non-apoptotic) unknown
    • Animal model recapitulation not demonstrated

Open questions

Synthesis pass · forward-looking unresolved questions
  • Key unresolved questions include the complete substrate repertoire of caspase-2, the structural basis of the full PIDDosome assembly, the mechanism by which CASP2 directly permeabilizes mitochondrial membranes, and how its apoptotic versus autophagy-suppressive functions are coordinated in vivo.
  • Full substrate spectrum not systematically mapped
  • Cryo-EM or crystal structure of intact PIDDosome with CASP2 absent
  • Whether CASP2-mediated autophagy suppression is relevant to the lissencephaly phenotype is untested

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0016787 hydrolase activity 4 GO:0140096 catalytic activity, acting on a protein 4
Localization
GO:0005634 nucleus 2 GO:0005794 Golgi apparatus 1
Pathway
R-HSA-5357801 Programmed Cell Death 7 R-HSA-9612973 Autophagy 2 R-HSA-1266738 Developmental Biology 1 R-HSA-8953897 Cellular responses to stimuli 1
Partners
ARCBIDCRADDGOLGA3PIDD1RIPK1
Complex memberships
PIDDosome (PIDD–RAIDD–CASP2)

Evidence

Reading pass · 26 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
1994 ICH-1L (the long form of CASP2) induces programmed cell death when overexpressed, while the alternatively spliced short form ICH-1S suppresses serum deprivation-induced cell death, demonstrating that CASP2 encodes both positive and negative regulators of apoptosis via alternative splicing. Overexpression in mammalian cells; serum deprivation apoptosis assay Cell High 8087842
1994 Nedd2/CASP2 overexpression induces apoptosis in fibroblast and neuroblastoma cells, and this death is suppressed by BCL-2, placing CASP2 downstream of BCL-2 in the programmed cell death pathway. Overexpression and genetic epistasis in cultured cells; BCL-2 co-expression rescue Genes & development High 7958843
1995 CASP2/Nedd2, together with ICE (CASP1), cleaves PARP in a manner identical to apoptotic cleavage; in vitro, recombinant ICE cleaves PARP in a time- and enzyme-concentration-dependent manner, though requiring 50–100-fold higher concentration than for IL-1β processing. COS cell co-transfection assay; in vitro cleavage with purified recombinant enzyme The Journal of biological chemistry High 7642516
1995 Antisense suppression of Nedd2/CASP2 in FDC-P1 cells significantly inhibits apoptosis upon cytokine withdrawal, demonstrating a direct role for CASP2 in mediating apoptosis. Antisense Nedd2 expression; cell death assay upon cytokine removal FEBS letters Medium 7615091
1996 The pro-Nedd2/CASP2 precursor (p51) is processed in vitro by CPP32 (caspase-3), ICE, and granzyme B into p19 and p12 subunits, indicating that CASP2 activation requires cleavage by upstream ICE-like proteases and that CASP2 may be a downstream effector in CTL-mediated killing. In vitro processing assay with purified caspases and granzyme B; cell extract processing assays Genes to cells High 9078393
1997 CASP2/Nedd2 is activated early during apoptosis induced by diverse stimuli, preceding caspase-3 (CPP32) activation, consistent with CASP2 being an upstream initiator caspase. Western blot detection of processed CASP2 in cells treated with apoptotic agents; temporal comparison with caspase-3 activation The Journal of biological chemistry Medium 9148927
1997 Nedd2/CASP2 is required for apoptosis induced by trophic factor withdrawal in PC12 cells and sympathetic neurons, but not for apoptosis caused by SOD1 downregulation, demonstrating stimulus-specific roles for distinct caspases. Antisense oligonucleotide knockdown; cell death and immunohistochemical assays in neurons and PC12 cells The Journal of neuroscience High 9045720
1997 RAIDD (CRADD) is an adaptor molecule that directly binds to caspase-2 via homophilic CARD–CARD (prodomain) interaction, and also binds to the death domain-containing kinase RIP, linking CASP2 to upstream death signaling pathways. Yeast two-hybrid and immunoprecipitation; domain mapping Nature High 8985253
1997 CRADD contains an N-terminal caspase homology domain that specifically interacts with caspase-2, and a C-terminal death domain that interacts with RIP, establishing CRADD as a bipartite adaptor bridging RIP and CASP2 in apoptotic signaling. Co-immunoprecipitation; domain deletion analysis; apoptosis assays Cancer research High 9044836
1998 The RAIDD CARD structure was solved by NMR and shown to consist of six helices arranged in a death-domain topology; mutagenesis of basic and acidic surface patches on opposite sides of RAIDD CARD and ICH-1/CASP2 CARD mediate their homophilic CARD–CARD interaction. NMR structure determination; mutagenesis; homology modeling Cell High 9695946
1998 The pro-Nedd2/CASP2 precursor dimerizes prior to autoprocessing; both the prodomain and C-terminal residues are required for dimerization, and dimerization occurs before cleavage of the catalytic subunits as shown in yeast. Yeast-based dimerization assay; aspartate-to-alanine mutants; in vitro processing by recombinant active Nedd2 The Journal of biological chemistry High 9506977
1998 The prodomain of CASP2 is required for nuclear localization of the precursor; GFP-fused prodomain alone localizes to nuclear dot- and fiber-like structures, and fusing the CASP2 prodomain to the normally cytoplasmic caspase-3 mediates its nuclear transport. GFP fusion constructs; live fluorescence microscopy; subcellular fractionation The Journal of biological chemistry High 9733748
1998 CASP2 processing at D333 occurs independently of caspase-3-like activity during trophic factor withdrawal; caspase-2 is required for death but caspase-3-like activity is neither necessary nor sufficient, placing CASP2 in a parallel or independent branch from caspase-3. Western blot for CASP2 processing; selective caspase inhibitors (DEVD-FMK vs BAF/zVAD); antisense to CASP2; enzymatic activity assays The Journal of neuroscience High 9801360
1998 ARC (apoptosis repressor with CARD) interacts selectively with caspase-2 (and caspase-8, CED-3) but not caspase-1, -3, or -9, via CARD–CARD interaction, and inhibits caspase-2-induced apoptosis; ARC is expressed primarily in skeletal muscle and heart. Immunoprecipitation; co-transfection apoptosis assays; enzymatic inhibition assay in 293T cells Proceedings of the National Academy of Sciences of the United States of America High 9560245
2000 Caspase-2 localizes to the Golgi complex (in addition to nucleus) and cleaves golgin-160 at a unique site not cleaved by other caspases with similar peptide specificities; prevention of this cleavage delays Golgi disintegration during apoptosis. Subcellular fractionation; immunofluorescence microscopy; in vitro cleavage assays; mutagenesis of golgin-160 cleavage site; apoptotic morphology assays The Journal of cell biology High 10791974
2002 Caspase-2 is required upstream of mitochondria for cytotoxic stress-induced apoptosis; it is activated before mitochondrial permeabilization and is necessary for cytochrome c release, establishing CASP2 as an initiator that acts upstream of the mitochondrial amplification step. Caspase-2 inhibitors and dominant-negative constructs; cytochrome c release assay; epistasis with mitochondrial pathway Science High 12193789
2002 Caspase-2 induces cytochrome c, AIF, and Smac release from isolated mitochondria independently of Bid or cytosolic factors; it also cleaves cytosolic Bid, which then triggers cytochrome c release; Bcl-2 and Bcl-xL block caspase-2-induced death; unlike caspase-8, caspase-2 cannot directly process other caspase zymogens. Purified recombinant caspase-2; isolated mitochondria assay; Bid cleavage in vitro; Bcl-2/Bcl-xL epistasis; substrate specificity panel The Journal of biological chemistry High 11832478
2002 Caspase-2 acts upstream of mitochondria in etoposide-induced apoptosis: inhibition of CASP2 (by z-VDVAD-fmk or antisense) blocks cytochrome c release and downstream caspase-9/-3 activation; the nuclear pool of pro-caspase-2 is critical for this process. Irreversible caspase-2 inhibitor; antisense stable transfection; cell-free reconstituted system; cytochrome c release assay The Journal of biological chemistry High 12065594
2004 Caspase-2 is activated within a large multiprotein complex called the PIDDosome, composed of PIDD (a p53-inducible death-domain protein) and the adaptor RAIDD; increased PIDD expression causes spontaneous caspase-2 activation and sensitizes cells to genotoxic stimuli. Co-immunoprecipitation of native complex; overexpression and knockdown; caspase-2 activity assays; genotoxic stress paradigm Science High 15073321
2005 PIDD plays distinct roles depending on complex composition: a PIDD–RAIDD–caspase-2 complex mediates apoptosis, while a separate PIDD–RIP1–NEMO complex activates NF-κB upon genotoxic stress; depletion of PIDD and RIP1 (but not caspase-2) abrogates DNA-damage-induced NEMO modification and NF-κB activation, demonstrating CASP2-independent PIDDosome signaling. RNAi knockdown; co-immunoprecipitation; NF-κB reporter assays; NEMO sumoylation/ubiquitination assays Cell High 16360037
2012 During sustained ER stress, IRE1α RNase cleaves microRNA precursors (miR-17, -34a, -96, -125b) that normally repress CASP2 mRNA translation, causing derepression of CASP2 protein expression and initiating the mitochondrial apoptotic pathway; recombinant IRE1α cleaves miRNA precursors at sites distinct from DICER. Cell-free IRE1α cleavage of miRNA precursors; ribosome profiling/translation assays; CASP2 protein quantification upon ER stress; epistasis with miRNA mimics/inhibitors Science High 23042294
2014 CASP2 is an endogenous repressor of autophagy; knockout or knockdown of CASP2 upregulates autophagy via AMPK–mTOR and AMPK–MAPK canonical pathways, and reinsertion of Casp2 in casp2−/− MEFs suppresses autophagy; enhanced ROS production downstream of CASP2 loss is an upstream event in autophagy induction. Casp2 knockout MEFs; Casp2 re-expression rescue; autophagy marker assays (LC3, p62); pathway inhibitors; ROS measurement Autophagy High 24879153
2014 Combined suppression of CASP2 (siRNA) and CASP6 (dominant-negative mutant) promotes retinal ganglion cell axon regeneration via activation of astrocytes and Müller cells, increased CNTF production, and JAK/STAT signaling; this regeneration is abrogated by CNTF receptor blockade or JAK/STAT inhibition. siRNA knockdown of CASP2; dominant-negative CASP6; optic nerve crush model; neutralizing antibody and kinase inhibitor epistasis; GFAP and CNTF immunostaining Brain Medium 24727569
2017 Rabies virus phosphoprotein binds BECN1, reducing CASP2 levels and activating CASP2-AMPK-AKT-mTOR and CASP2-AMPK-MAPK pathways, thereby inducing incomplete autophagy (autophagosome accumulation with impaired flux). Co-immunoprecipitation of BECN1 with viral P protein; CASP2 knockdown/overexpression; autophagy flux assays; AMPK/mTOR/MAPK pathway inhibitors Autophagy Medium 28129024
2023 Biallelic truncating variants in CASP2 cause a neurodevelopmental disorder with anterior-predominant lissencephaly and pachygyria, establishing CASP2 as an essential component of the PIDDosome required for normal cerebral cortex development; the phenotype resembles CRADD- and PIDD1-related disorders. Exome sequencing; RNA splicing studies of splice-site variant; clinical and neuroimaging phenotyping across 7 patients from 5 families European journal of human genetics Medium 37880421
2024 CCN1 upregulates CASP2 transcription via an RB1/E2F1 mechanism (by downregulating p16 and p21 to increase RB1 phosphorylation) but simultaneously upregulates HuR which binds CASP2 mRNA and blocks its translation, so CASP2 protein does not increase and does not contribute to CCN1-induced apoptosis in esophageal adenocarcinoma cells. Reporter assays; western blot; RNAi knockdown of RB1, E2F1, HuR; RNA immunoprecipitation for HuR-CASP2 mRNA binding; CASP2 overexpression rescue Journal of cell communication and signaling Medium 39524140

Source papers

Stage 0 corpus · 73 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
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
2017 Architecture of the human interactome defines protein communities and disease networks. Nature 1085 28514442
2014 A proteome-scale map of the human interactome network. Cell 977 25416956
2020 A reference map of the human binary protein interactome. Nature 849 32296183
1994 Ich-1, an Ice/ced-3-related gene, encodes both positive and negative regulators of programmed cell death. Cell 822 8087842
2003 Complete sequencing and characterization of 21,243 full-length human cDNAs. Nature genetics 754 14702039
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
1999 Nod1, an Apaf-1-like activator of caspase-9 and nuclear factor-kappaB. The Journal of biological chemistry 621 10329646
1994 Induction of apoptosis by the mouse Nedd2 gene, which encodes a protein similar to the product of the Caenorhabditis elegans cell death gene ced-3 and the mammalian IL-1 beta-converting enzyme. Genes & development 600 7958843
2002 Requirement for caspase-2 in stress-induced apoptosis before mitochondrial permeabilization. Science (New York, N.Y.) 592 12193789
2012 IRE1α cleaves select microRNAs during ER stress to derepress translation of proapoptotic Caspase-2. Science (New York, N.Y.) 550 23042294
2004 The PIDDosome, a protein complex implicated in activation of caspase-2 in response to genotoxic stress. Science (New York, N.Y.) 531 15073321
1994 Crystal structure of the cysteine protease interleukin-1 beta-converting enzyme: a (p20/p10)2 homodimer. Cell 517 8044845
1996 Molecular ordering of the Fas-apoptotic pathway: the Fas/APO-1 protease Mch5 is a CrmA-inhibitable protease that activates multiple Ced-3/ICE-like cysteine proteases. Proceedings of the National Academy of Sciences of the United States of America 489 8962078
2008 Executioner caspase-3 and caspase-7 are functionally distinct proteases. Proceedings of the National Academy of Sciences of the United States of America 459 18723680
1997 RAIDD is a new 'death' adaptor molecule. Nature 455 8985253
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
2002 Caspase-2 induces apoptosis by releasing proapoptotic proteins from mitochondria. The Journal of biological chemistry 427 11832478
2016 Widespread Expansion of Protein Interaction Capabilities by Alternative Splicing. Cell 423 26871637
2005 Diversification of transcriptional modulation: large-scale identification and characterization of putative alternative promoters of human genes. Genome research 409 16344560
2002 Caspase-2 acts upstream of mitochondria to promote cytochrome c release during etoposide-induced apoptosis. The Journal of biological chemistry 334 12065594
2000 Caspase-2 is localized at the Golgi complex and cleaves golgin-160 during apoptosis. The Journal of cell biology 320 10791974
1998 ARC, an inhibitor of apoptosis expressed in skeletal muscle and heart that interacts selectively with caspases. Proceedings of the National Academy of Sciences of the United States of America 301 9560245
1997 FLAME-1, a novel FADD-like anti-apoptotic molecule that regulates Fas/TNFR1-induced apoptosis. The Journal of biological chemistry 287 9228018
2005 PIDD mediates NF-kappaB activation in response to DNA damage. Cell 284 16360037
1998 Solution structure of the RAIDD CARD and model for CARD/CARD interaction in caspase-2 and caspase-9 recruitment. Cell 272 9695946
2011 A directed protein interaction network for investigating intracellular signal transduction. Science signaling 258 21900206
1998 Alteration of proteins regulating apoptosis, Bcl-2, Bcl-x, Bax, Bak, Bad, ICH-1 and CPP32, in Alzheimer's disease. Brain research 226 9507158
1997 CRADD, a novel human apoptotic adaptor molecule for caspase-2, and FasL/tumor necrosis factor receptor-interacting protein RIP. Cancer research 225 9044836
2011 Toward an understanding of the protein interaction network of the human liver. Molecular systems biology 207 21988832
1995 Cleavage of poly(ADP-ribose) polymerase by interleukin-1 beta converting enzyme and its homologs TX and Nedd-2. The Journal of biological chemistry 161 7642516
1997 Nedd2 is required for apoptosis after trophic factor withdrawal, but not superoxide dismutase (SOD1) downregulation, in sympathetic neurons and PC12 cells. The Journal of neuroscience : the official journal of the Society for Neuroscience 145 9045720
1998 Prodomain-dependent nuclear localization of the caspase-2 (Nedd2) precursor. A novel function for a caspase prodomain. The Journal of biological chemistry 139 9733748
1997 Functional activation of Nedd2/ICH-1 (caspase-2) is an early process in apoptosis. The Journal of biological chemistry 130 9148927
2005 T25 repeat in the 3' untranslated region of the CASP2 gene: a sensitive and specific marker for microsatellite instability in colorectal cancer. Cancer research 123 16166278
1998 Dimerization and autoprocessing of the Nedd2 (caspase-2) precursor requires both the prodomain and the carboxyl-terminal regions. The Journal of biological chemistry 100 9506977
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 Evaluation of the CASP2 docking section. Proteins 62 9485512
2014 A nonapoptotic role for CASP2/caspase 2: modulation of autophagy. Autophagy 61 24879153
2014 Combined suppression of CASP2 and CASP6 protects retinal ganglion cells from apoptosis and promotes axon regeneration through CNTF-mediated JAK/STAT signalling. Brain : a journal of neurology 57 24727569
1996 Processing of the Nedd2 precursor by ICE-like proteases and granzyme B. Genes to cells : devoted to molecular & cellular mechanisms 57 9078393
1997 Inhibitors of trypsin-like serine proteases inhibit processing of the caspase Nedd-2 and protect PC12 cells and sympathetic neurons from death evoked by withdrawal of trophic support. Journal of neurochemistry 56 9326271
2017 BECN1-dependent CASP2 incomplete autophagy induction by binding to rabies virus phosphoprotein. Autophagy 55 28129024
2000 Tumor necrosis factor-alpha-induced apoptosis in olfactory epithelium in vitro: possible roles of caspase 1 (ICE), caspase 2 (ICH-1), and caspase 3 (CPP32). Experimental neurology 55 10964483
1997 Up-regulation of the Nedd2 gene encoding an ICE/Ced-3-like cysteine protease in the gerbil brain after transient global ischemia. Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism 55 9183288
1995 Inhibition of apoptosis by the expression of antisense Nedd2. FEBS letters 55 7615091
2022 miR-150-3p enhances neuroprotective effects of neural stem cell exosomes after hypoxic-ischemic brain injury by targeting CASP2. Neuroscience letters 50 35436510
1998 The ich1 gene of the mushroom Coprinus cinereus is essential for pileus formation in fruiting. Development (Cambridge, England) 46 9671586
1997 Meeting review: the Second meeting on the Critical Assessment of Techniques for Protein Structure Prediction (CASP2), Asilomar, California, December 13-16, 1996. Folding & design 43 9135979
1997 CASP2: report on ab initio predictions. Proteins 40 9485507
1995 Apoptosis regulatory gene NEDD2 maps to human chromosome segment 7q34-35, a region frequently affected in haematological neoplasms. Human genetics 38 7789948
1997 CASP2 experiences with docking flexible ligands using FlexX. Proteins 37 9485516
2017 Aging and calorie restriction regulate the expression of miR-125a-5p and its target genes Stat3, Casp2 and Stard13. Aging 31 28783714
2019 MiR-494 acts as a tumor promoter by targeting CASP2 in non-small cell lung cancer. Scientific reports 30 30816202
1996 Chromosomal localization of the human genes, CPP32, Mch2, Mch3, and Ich-1, involved in cellular apoptosis. Biochemical and biophysical research communications 22 8780721
1997 A retrospective analysis of CASP2 threading predictions. Proteins 19 9485499
2001 CASP2 knowledge-based approach to distant homology recognition and fold prediction in CASP4. Proteins 18 11835484
1997 Characterization of the avian Ich-1 cDNA and expression of Ich-1L mRNA in the hen ovary. Gene 17 9224894
2000 Reactivation of Nedd-2, a developmentally down-regulated apoptotic gene, in apoptosis induced by a street strain of rabies virus. Journal of medical microbiology 16 11073159
1997 Cysteine protease CPP32, but not Ich1-L, is expressed in germinal center B cells and their neoplastic counterparts. Human pathology 16 9269827
1997 Blind predictions of local protein structure in CASP2 targets using the I-sites library. Proteins 15 9485508
1997 CASP2 molecular docking predictions with the LIGIN software. Proteins 15 9485514
1997 Fold assignments for amino acid sequences of the CASP2 experiment. Proteins 14 9485502
1998 Expression of Nedd2/ICH-1 (caspase-2) in the developing rat retina. Neuroscience research 12 9809666
2023 Bi-allelic truncating variants in CASP2 underlie a neurodevelopmental disorder with lissencephaly. European journal of human genetics : EJHG 11 37880421
1997 Characterization of a mammalian cell death gene Nedd2. Leukemia 11 9209399
2022 MiR-17-5p protects neonatal mice from hypoxic-ischemic brain damage by targeting Casp2. Neuroscience letters 9 35085690
2024 PANoptosis-related molecule CASP2 affects the immune microenvironment and immunotherapy response of hepatocellular carcinoma. Heliyon 6 38509889
2024 Cellular communication network 1 promotes CASP2 mRNA expression but suppresses its protein translation in esophageal adenocarcinoma. Journal of cell communication and signaling 1 39524140
2002 [Relationship between hepatitis C virus infection and expression of apoptosis-related gene bcl-2, bax and ICH-1 in hepatocellular carcinoma tissues]. Di 1 jun yi da xue xue bao = Academic journal of the first medical college of PLA 1 12297434