Affinage

BID

BH3-interacting domain death agonist · UniProt P55957

Length
195 aa
Mass
22.0 kDa
Annotated
2026-06-09
100 papers in source corpus 38 papers cited in narrative 37 extracted findings
Cross-family judge vs UniProt: Affinage preferred faithfulness: 9/9 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

BID is a BH3-only BCL-2 family protein that functions as the principal molecular bridge coupling proteolytic death signals to mitochondrial outer-membrane permeabilization (MOMP) and apoptosis (PMID:9727491, PMID:8918887). Cytosolic full-length BID is cleaved by caspase-8 to yield a C-terminal fragment (tBid) that translocates to mitochondria and triggers cytochrome c release; an intact BH3 domain and Bcl-2 antagonism define this as a canonical apoptotic switch (PMID:9727491, PMID:8918887). Diverse proteases converge on BID to generate active tBid—granzyme B during cytotoxic-lymphocyte killing (PMID:11114298, PMID:15574417), calpains during cisplatin treatment and AIF-mediated necroptosis (PMID:11940658, PMID:21738214), lysosomal cathepsins (PMID:18469004), and caspase-1 during inflammatory secondary necrosis (PMID:32345661)—establishing BID as a shared effector node for extrinsic, lysosomal, and inflammatory death routes. Together with BIM and PUMA, BID is an essential direct activator of BAX and BAK, and BID-deficient or triple-knockout cells fail to oligomerize BAX/BAK or release cytochrome c (PMID:21127253, PMID:24074954). At the membrane, tBid inserts via its synergistic α6–α7 hydrophobic hairpin (PMID:27053107, PMID:15323553), engages MTCH2 in a primed state, and then activates BAK at its canonical BH3-binding groove through a 'hit-and-run' mechanism that permits BAK homo-oligomerization and MOMP (PMID:23604079, PMID:33462413), with BID preferentially activating BAK over BAX (PMID:24074954). BID activity acts strictly on the outer membrane to release cytochrome c, SMAC, and AIF, driving both caspase-dependent and caspase-independent death (PMID:10973993, PMID:18535584). BID expression is induced as a p53 transcriptional target (PMID:12402042) and repressed by PLZF (PMID:14769944), while phosphorylation by casein kinases I/II protects it from caspase-8 cleavage and tempers death-receptor signaling (PMID:11583622, PMID:20356928). Beyond apoptosis, ATM-dependent phosphorylation directs nuclear BID into the ATR/ATRIP/RPA replication-stress sensor complex—where it binds the RPA70 N-terminal cleft to support CHK1 activation and S-phase checkpoint recovery (PMID:16122425, PMID:16122426, PMID:21859891, PMID:21113148)—and this DNA-damage-response function maintains haematopoietic stem cell quiescence and limits mitochondrial oxidative stress (PMID:22446738). BID also participates in NOD1/NOD2–IKK innate-immune signaling (PMID:21552281) and is required for mitochondrial dysfunction in ferroptosis (PMID:28384611), extending its role beyond classical cell death.

Mechanistic history

Synthesis pass · year-by-year structured walk · 15 steps
  1. 1996 High

    Established BID as a BH3-only protein whose death-promoting activity is separable from its physical interactions, defining the structural basis of its function.

    Evidence Yeast two-hybrid cloning, BH3 mutagenesis, and co-immunoprecipitation showing BH3-dependent binding to BAX and BCL-2

    PMID:8918887

    Open questions at the time
    • Did not define the upstream activator that processes BID
    • Mechanism of BAX/BCL-2 binding versus death promotion left unresolved
  2. 1998 High

    Answered how the extrinsic and intrinsic pathways connect by showing caspase-8 cleaves BID into tBid that triggers mitochondrial cytochrome c release.

    Evidence In vitro caspase cleavage, immunodepletion, BH3 mutagenesis, and cell-free cytochrome c release assay

    PMID:9727491

    Open questions at the time
    • How tBid permeabilizes the membrane was not resolved
    • Whether other proteases activate BID was unknown
  3. 2000 High

    Defined the membrane target of BID by showing recombinant BID/BAX act only on the outer mitochondrial membrane, sparing inner-membrane function.

    Evidence Isolated mitochondria assays with EM ultrastructure and protein-import readouts; cell-free granzyme B reconstitution with immunodepletion

    PMID:10973993 PMID:11114298

    Open questions at the time
    • Required mitochondrial co-factors for BAX oligomerization not identified
    • Channel-forming versus pore-inducing mechanism unresolved
  4. 2001 High

    Showed that casein kinase phosphorylation gates BID's susceptibility to caspase-8 cleavage, establishing post-translational control of the death switch.

    Evidence In vitro kinase assay, phospho-mutant mutagenesis, and pharmacological CKI/CKII inhibition in Fas apoptosis

    PMID:11583622

    Open questions at the time
    • Kinetic coupling to caspase-8 in living cells not yet measured
    • Physiological signals controlling CKI/CKII activity on BID unknown
  5. 2002 High

    Broadened BID activation beyond caspases by identifying calpain cleavage and p53-dependent transcriptional induction as alternative routes to BID activity.

    Evidence In vitro calpain cleavage with site mapping and inhibitor panels; p53 response-element reporter and BID-null MEF chemoresistance

    PMID:11940658 PMID:12402042

    Open questions at the time
    • p53 transactivation evidence is Medium-confidence and single-lab
    • Relative in vivo contribution of calpain versus caspase cleavage unclear
  6. 2004 Medium

    Demonstrated that DNA-damage-induced BID cleavage can occur independently of death-receptor or known mitochondrial caspases, hinting at a distinct stress-response role.

    Evidence Dominant-negative caspases, CrmA, caspase-2 siRNA, and cleavage-site mapping in p53-mutant leukemic cells; granzyme B species-specificity profiling

    PMID:15117953 PMID:17179148

    Open questions at the time
    • Identity of the protease cleaving BID after DNA damage not defined
    • Mouse granzyme B resistance limits mouse-model interpretation
  7. 2005 High

    Revealed a non-apoptotic nuclear function: ATM phosphorylates BID after double-strand breaks to enforce S-phase arrest, separating BID's DNA-damage role from its death role.

    Evidence Phospho-mapping, ATM kinase assay, Bid-/- reconstitution with phospho-mutants, cell-cycle analysis, and nuclear fractionation; PACS-2-dependent mitochondrial translocation

    PMID:15692567 PMID:16122425 PMID:16122426

    Open questions at the time
    • Molecular target of nuclear BID at the checkpoint not yet identified
    • PACS-2 translocation evidence is Medium-confidence single-lab
  8. 2008 Medium

    Extended BID's protease repertoire to lysosomal cathepsins and established BID as the link between mitochondria and caspase-independent AIF-driven neuronal death.

    Evidence In vitro cathepsin cleavage with E-64d; live imaging and siRNA epistasis placing AIF downstream of BID

    PMID:18469004 PMID:18535584

    Open questions at the time
    • Cathepsin cleavage sites in cells not mapped
    • AIF-pathway evidence rests on siRNA in a single neuronal system
  9. 2010 High

    Defined BID as a genetically essential direct activator of BAX/BAK and placed it at the ATR damage-sensor complex during replicative stress.

    Evidence Triple-knockout mouse epistasis with oligomerization assays; nuclear foci colocalization and Co-IP of BID with ATR/ATRIP/RPA in Bid-/- cells; single-cell CK2 kinetics

    PMID:20356928 PMID:21113148 PMID:21127253

    Open questions at the time
    • Direct activator role does not exclude redundancy with BIM/PUMA in specific tissues
    • Precise step of ATR-complex assembly stimulated by BID not yet defined
  10. 2011 High

    Mapped BID's nuclear interaction surface to RPA70 and uncovered roles in NOD innate immunity and calpain-driven necroptosis, expanding its functional range.

    Evidence NMR-guided BID-RPA70 mapping with functional mutants; genome-wide RNAi and reciprocal Co-IP with NOD1/NOD2/IKK plus in vivo colitis; calpain-resistant BID mutant rescue in necroptosis

    PMID:21552281 PMID:21738214 PMID:21859891

    Open questions at the time
    • How a single protein partitions between mitochondrial, nuclear, and IKK pools is unresolved
    • Whether NOD/IKK function requires BID cleavage is unclear
  11. 2012 High

    Showed that ATM-BID phosphorylation maintains haematopoietic stem cell quiescence and limits mitochondrial ROS, giving the DNA-damage function an in vivo physiological output.

    Evidence Knock-in phospho-mutant mice with quiescence, competitive reconstitution, ROS, and irradiation-survival assays

    PMID:22446738

    Open questions at the time
    • Mechanism linking BID phosphorylation to mitochondrial ROS control not defined
    • Connection between nuclear checkpoint role and stem-cell phenotype incompletely mapped
  12. 2013 High

    Provided the structural and selectivity logic of BID-mediated activation: a 'hit-and-run' engagement of the BAK BH3 groove and a preference for BAK over BAX.

    Evidence NMR structure of BID BH3–BAK with BH1/BH3 mutagenesis and MOMP assays; BH3 profiling across BAK/BAX-knockout lines

    PMID:23604079 PMID:24074954

    Open questions at the time
    • Structural basis of BAK-over-BAX preference not fully explained
    • Transient nature of the trigger interaction limits direct visualization
  13. 2016 High

    Confirmed caspase-8 as the primary physiological activator during TRAIL apoptosis and showed the α6–α7 helices anchor tBid to mitochondria for full activity.

    Evidence CRISPR BID-KO and BID/BAX/BAK TKO reconstitution with caspase-resistant, BH3-defective, and helix-deletion mutants; live-cell FRET of BID-BAX contacts

    PMID:27053107 PMID:27763642

    Open questions at the time
    • Role of effector caspases in BID activation excluded only in the TRAIL context
    • Live-cell FRET (Medium) needs corroboration of oligomer stoichiometry
  14. 2020 Medium

    Linked BID to inflammatory cell death by showing caspase-1 cleaves BID to drive SMAC release and secondary necrosis when GSDMD is absent.

    Evidence GSDMD-/- and GSDMD/BID double-knockout cells with caspase and SMAC-release assays

    PMID:32345661

    Open questions at the time
    • Single-lab study without in vivo validation
    • Physiological settings where caspase-1–BID axis dominates not defined
  15. 2021 High

    Resolved the stepwise membrane activation pathway, showing membrane-bound cBid exposes its BH3 domain, associates with MTCH2, and remains primed until BAX-triggered fragmentation.

    Evidence Spin-label ESR, site-directed PEGylation at authentic mitochondrial membranes, and Co-IP with MTCH2

    PMID:33462413

    Open questions at the time
    • Functional consequence of MTCH2 association in vivo not established
    • How the primed state is released specifically by BAX versus BAK unclear

Open questions

Synthesis pass · forward-looking unresolved questions
  • How a single BID protein is partitioned and regulated across its mitochondrial death, nuclear checkpoint, innate-immune, and ferroptosis functions—and what determines which output dominates in a given cell—remains unresolved.
  • No unifying model coordinating cytosolic, mitochondrial, and nuclear BID pools
  • Determinants of protease and partner selection in different stress contexts not defined

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0098772 molecular function regulator activity 4 GO:0140313 molecular sequestering activity 3 GO:0060090 molecular adaptor activity 2 GO:0008289 lipid binding 1
Localization
GO:0005634 nucleus 3 GO:0005739 mitochondrion 3 GO:0005829 cytosol 2
Pathway
R-HSA-5357801 Programmed Cell Death 5 R-HSA-168256 Immune System 3 R-HSA-73894 DNA Repair 3 R-HSA-8953897 Cellular responses to stimuli 2
Partners
AIFBAKBAXBCL-2MTCH2NOD2PACS-2RPA70
Complex memberships
ATR/ATRIP/RPA replication-stress sensor complex

Evidence

Reading pass · 37 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
1998 Caspase-8 cleaves BID, and the C-terminal fragment (tBid) translocates to mitochondria where it triggers cytochrome c release; immunodepletion of BID eliminated cytochrome c releasing activity; a BH3 domain mutation diminished activity; Bcl2 antagonized tBid activity Protein purification, peptide mass fingerprinting, in vitro caspase cleavage assay, immunodepletion, site-directed mutagenesis, cell-free cytochrome c release assay Cell High 9727491
1996 BID is a BH3-only protein that heterodimerizes with both BAX and BCL-2 via its BH3 domain; an intact BH3 domain is required to bind the BH1 domain of BCL-2 or BAX; BH3 mutagenesis dissociated binding from death-promoting activity; BID expression induces ICE-like proteases and apoptosis Interactive (yeast two-hybrid) cloning, site-directed mutagenesis, co-immunoprecipitation, cell death assays Genes & development High 8918887
2001 BID is phosphorylated by casein kinase I (CKI) and casein kinase II (CKII); phosphorylated BID is insensitive to caspase-8 cleavage in vitro; inhibition of CKI/CKII accelerated Fas-mediated apoptosis and BID cleavage; a non-phosphorylatable BID mutant was more toxic than wild-type In vitro kinase assay, site-directed mutagenesis, pharmacological kinase inhibition, Fas-mediated apoptosis assays Molecular cell High 11583622
2005 BID is phosphorylated by ATM kinase following DNA double-strand breaks on two ATM consensus sites; BID-deficient cells fail to accumulate in S phase after etoposide treatment; a non-phosphorylatable BID mutant did not restore S phase arrest and increased sensitivity to etoposide-induced apoptosis; BID partially localizes to the nucleus in healthy cells Phosphorylation mapping, ATM kinase assay, Bid-/- cell reconstitution with wild-type vs. phospho-mutant BID, cell cycle analysis, nuclear fractionation Cell High 16122425 16122426
2005 PACS-2 translocates BID to mitochondria in response to apoptotic inducers, initiating tBid formation, cytochrome c release, and caspase-3 activation; depletion of PACS-2 prevents BID-mediated apoptosis siRNA knockdown, subcellular fractionation, Western blot for tBid/cytochrome c/caspase-3, live-cell imaging of mitochondria-ER contacts The EMBO journal Medium 15692567
2010 BID, BIM, and PUMA are essential activators of BAX and BAK; triple knockout of Bid/Bim/Puma phenocopies Bax/Bak double knockout (persistent interdigital webs, imperforate vaginas) and prevents BAX/BAK homo-oligomerization and cytochrome c release in neurons and T lymphocytes Triple-knockout mouse genetics, epistasis analysis, cytochrome c release assay, BAX/BAK oligomerization assay Science High 21127253
2013 NMR solution structure of the human BID BH3–BAK complex identified the activation site at the canonical BH3-binding groove of BAK; BAK BH1 groove mutations prevented MOMP but not BID binding; BAK BH3 mutations allowed BID binding but blocked oligomerization; BID follows a 'hit-and-run' mechanism dissociating from the trigger site to allow BAK oligomerization; NOXA and BAD are predicted to clash with the trigger site and are not activators of BAK NMR structure determination, site-directed mutagenesis of BAK BH1 and BH3 domains, MOMP assay, binding assay Nature structural & molecular biology High 23604079
2013 BID preferentially activates BAK while BIM preferentially activates BAX; cells lacking BAK are relatively resistant to agents requiring BID activation (topoisomerase inhibitors, TRAIL) BH3 profiling, BAK/BAX knockout cell lines, apoptosis assays, clinical correlation Molecular cell High 24074954
2002 Calpain cleaves BID between Gly70 and Arg71 in cisplatin-treated cells, yielding a 14-kDa fragment; calpain-cleaved BID induces cytochrome c release from isolated mitochondria; calpain inhibitors but not caspase or cathepsin L inhibitors prevented BID cleavage In vitro calpain cleavage of recombinant BID, cleavage site mapping, isolated mitochondria cytochrome c release assay, pharmacological inhibitor panel Molecular and cellular biology High 11940658
2000 Granzyme B cleaves cytosolic BID to produce truncated BID, which is the sole cytosolic protein responsible for GrB-induced cytochrome c release in a cell-free system; GrB also acts directly on mitochondria to open the permeability transition pore independently of cytosolic proteins Cell-free in vitro system, immunodepletion, recombinant protein assays, mitochondrial membrane potential measurement The Journal of biological chemistry High 11114298
2004 Bid-deficient cells from multiple tissues are resistant to granzyme B-induced cell death; cytochrome c remains in mitochondria of Bid-deficient cells treated with granzyme B; surviving Bid-deficient cells proliferate normally Bid-/- mouse-derived primary cells, granzyme B treatment, cytochrome c localization by fractionation, cell viability and proliferation assays The Journal of biological chemistry High 15574417
2008 Lysosomal cysteine cathepsins (B, L, S, K, H) cleave BID in vitro; cathepsin-mediated BID cleavage triggers the mitochondrial apoptosis pathway; E-64d (cysteine protease inhibitor) prevented BID cleavage and apoptosis In vitro protease cleavage assays with purified cathepsins and recombinant BID, pharmacological inhibitor studies, cell death assays The Journal of biological chemistry High 18469004
2002 BID is a p53 transcriptional target; the human and mouse BID genomic loci contain p53-binding DNA response elements that bind p53 and mediate p53-dependent transactivation; BID-null MEFs are more resistant to adriamycin and 5-fluorouracil Reporter gene assay with p53 response elements, chromatin immunoprecipitation-like binding assay, BID-null MEF apoptosis assays Nature cell biology Medium 12402042
2011 BID interacts with NOD1, NOD2, and the IKK complex, impacting NF-κB and ERK signaling; BID-deficient colonocytes and macrophages are markedly defective in cytokine production in response to NOD activation; Bid-/- mice are unresponsive to NOD agonists in experimental colitis Genome-wide RNAi screen, co-immunoprecipitation of BID with NOD1/NOD2/IKK, Bid-/- macrophage cytokine assays, in vivo colitis model Nature High 21552281
2000 Recombinant BID and Bax cause complete cytochrome c loss from isolated mitochondria in vitro while preserving inner membrane ultrastructure and protein import function; BID and BAX act only on the outer mitochondrial membrane; inner membrane lesions during apoptosis are secondary caspase-dependent events Isolated mitochondria in vitro assay, electron microscopy of ultrastructure, mitochondrial protein import assay, caspase inhibition experiments The Journal of cell biology High 10973993
2000 BID-induced mitochondrial membrane permeabilization can be inhibited by PTPC inhibitors (cyclosporin A, bongkrekic acid); full-length BID preferentially permeabilizes membranes containing both ANT and BAX; tBid acts on membranes containing ANT alone, suggesting functional interaction with ANT (adenine nucleotide translocase) Intact cell microinjection, isolated mitochondria assay, proteoliposome reconstitution, planar bilayer electrophysiology Oncogene Medium 11175349
2002 tBid requires interaction with BAX and the BAX C-terminal transmembrane domain to induce ionic channel formation in liposomes; cut BID alone cannot induce BAX oligomerization in liposomes; an additional mitochondrial factor is required for BAX oligomerization Liposome reconstitution, planar bilayer electrophysiology, gel filtration, recombinant protein interaction assays The Biochemical journal Medium 11964155
2016 Cleavage by caspase-8 (not effector caspases) is the primary event activating BID during TRAIL-induced apoptosis; additionally, association of tBid with the outer mitochondrial membrane via helices α6 and α7 is required for full apoptotic activity; a tBid mutant lacking these helices has diminished activity despite an intact BH3 domain CRISPR/Cas9 BID-KO and BID/BAX/BAK TKO cells, reconstitution with wild-type and caspase-resistant/BH3-defective/helix-deletion mutants, TRAIL apoptosis assay The Journal of biological chemistry High 27053107
2011 BID controls BAX activation in AIF-mediated caspase-independent necroptosis; BID is processed by calpains into tBid (non-cleavable BID-G70A or BID-Δ68-71 abolishes BAX activation); tBid localizes to mitochondria to facilitate BAX activation and programmed necrotic death Bid-/- and calpain-resistant BID mutant MEFs, BAX activation assay, necroptosis (MNNG) model, reintroduction of wild-type vs. mutant BID Cell death and differentiation High 21738214
2012 ATM-mediated BID phosphorylation maintains quiescence of haematopoietic stem cells (HSCs); loss of BID phosphorylation leads to escape from quiescence, HSC pool exhaustion, and reduced repopulating potential; BID phosphorylation protects HSCs from irradiation by regulating oxidative stress; loss of phosphorylation or ATM knockout increases mitochondrial BID correlating with increased mitochondrial ROS Knock-in phospho-mutant BID mice, HSC quiescence assays (BrdU), competitive reconstitution assays, ROS measurement, irradiation survival Nature cell biology High 22446738
2011 BID associates with RPA70 N-terminal basic cleft; BID stimulates association of RPA with ATR-ATRIP complex; disruption of BID-RPA interaction impairs ATR-ATRIP chromatin association, CHK1 activation, and recovery of DNA replication following hydroxyurea Co-immunoprecipitation, NMR mapping of BID-RPA70 interaction, BID mutants disrupting RPA binding, chromatin fractionation, CHK1 phosphorylation assay, DNA replication recovery assay Molecular and cellular biology High 21859891
2010 BID functions at the level of the ATR damage sensor complex following replicative stress; BID is found in nuclear foci with RPA and associates with ATR/ATRIP/RPA complex; BID-deficient cells show reduced ATR/ATRIP chromatin loading, reduced CHK1 activation, and impaired recovery of DNA synthesis Nuclear foci colocalization, co-immunoprecipitation of BID with ATR/ATRIP/RPA, Bid-/- cell chromatin fractionation, CHK1 phosphorylation assay Cell death and differentiation High 21113148
2005 Humanin (HN) peptide binds purified BID and tBid in vitro; HN blocks tBid-induced cytochrome c and SMAC release from isolated mitochondria; HN inhibits tBid-induced BAX and BAK oligomerization in mitochondrial membranes; inactive HN mutants fail to bind BID or block these activities In vitro binding assay with purified proteins, isolated mitochondria cytochrome c/SMAC release assay, chemical cross-linking/gel filtration for oligomerization, gene transfection The Journal of biological chemistry Medium 15661737
2004 Membrane-insertion analysis shows that the α6 helix of tBid inserts into membranes only as part of the α6-α7 hairpin (not individually), indicating synergistic hairpin insertion into mitochondrial membrane is required for function Glycosylation mapping of chimeric single-helix segments in a model membrane insertion system Biochemistry Medium 15323553
2021 Stepwise activation of cBid at real mitochondrial membranes: upon mitochondrial binding, cBid reorganizes to expose the BH3 domain while maintaining overall structural integrity; membrane-bound cBid associates with MTCH2 and remains primed until interacting with BAX, which triggers cBid fragmentation, large conformational changes, and BAX-mediated MOMP Spin-label ESR spectroscopy, site-directed PEGylation at real mitochondrial membranes, co-immunoprecipitation with MTCH2 Cell death and differentiation High 33462413
2016 In live cells, BID adopts an extended conformation at the mitochondrial outer membrane critical for its association with the membrane and for intermolecular contacts within BID oligomers; direct intermolecular FRET contacts between BID and BAX were observed in live cells, confirming BID as a component of the BID-BAX permeabilization network Confocal FRET microscopy in live cells, FRET efficiency measurement, conformational analysis Cell death & disease Medium 27763642
2003 Three novel BID isoforms are generated by alternative splicing: BidS (lacks BH3 domain, inhibits tBid pro-apoptotic effects and Fas-mediated apoptosis), BidEL (induces apoptosis), and BidES (induces apoptosis but partially inhibits tBid); expression of these isoforms is regulated during granulocyte maturation and they differ in subcellular localization RT-PCR/gene structure analysis, endogenous protein detection, cell death assays, subcellular localization The Journal of biological chemistry Medium 14583606
2017 BID translocates to mitochondria during erastin-induced ferroptosis; CRISPR/Cas9 Bid knockout preserves mitochondrial integrity and function, and mediates neuroprotection against ferroptosis and oxytosis; BID inhibitor BI-6c9 inhibited ferroptosis; ferroptosis inhibitors (ferrostatin-1, liproxstatin-1) prevented BID-dependent mitochondrial dysfunction CRISPR/Cas9 BID knockout, mitochondrial membrane potential measurement, ATP assay, mitochondrial fragmentation imaging, pharmacological inhibitors Redox biology Medium 28384611
2020 Caspase-1 directly cleaves BID to generate tBid; in GSDMD-deficient cells, tBid-induced MOMP drives SMAC release to relieve IAP inhibition of caspase-3, enabling rapid secondary necrosis; caspase-1-driven activation of caspase-8/-9 and Bid cleavage act synergistically GSDMD-/- and GSDMD/BID double-KO cells, caspase activation assays, SMAC release measurement, caspase-1 cleavage assay Life science alliance Medium 32345661
2008 BID translocation to mitochondria precedes AIF release; BID-mediated mitochondrial AIF release causes rapid nuclear translocation and caspase-independent neuronal death; BID siRNA and BID inhibitor prevented AIF nuclear translocation and cell death; tBid-induced death was inhibited by AIF siRNA, establishing AIF as the main downstream effector of BID in glutamate-induced neuronal death Fluorescence video microscopy, BID siRNA, small molecule BID inhibitor, AIF siRNA, caspase-3 inhibitor comparison Cell death and differentiation Medium 18535584
2002 BID sequence has significant similarity to plant lipid transfer proteins; isolated BID shows lipid transfer activity higher than plant LTPs; lysolipids alter BID association with mitochondria and stimulate BID-induced cytochrome c release; BID enhances incorporation of fluorescent lysolipids into mitochondria Sequence analysis, in vitro lipid transfer assay, isolated mitochondria cytochrome c release assay with exogenous lipids, fluorescent lipid incorporation assay Biochimica et biophysica acta Medium 11997142
2010 Activity of protein kinase CK2 temporally uncouples caspase-8 activation from BID cleavage during TRAIL-induced apoptosis; CK2 inhibition (DRB) or dominant-negative CK2α largely eliminated the lag time between caspase-8 activation and BID cleavage in individual cells Single-cell FRET probes for caspase-8 (IETD) and full-length BID, CK2 inhibitor and dominant-negative expression, time-lapse microscopy Journal of cell science Medium 20356928
2006 PLZF transcription factor binds a high-affinity site upstream of the BID transcriptional start site (EMSA) and represses BID expression; PLZF-expressing Jurkat cells show retarded mitochondrial membrane potential loss and resistance to apoptosis Differential expression screen, EMSA for PLZF binding to BID promoter, inducible PLZF expression, annexin V/TUNEL apoptosis assays Proceedings of the National Academy of Sciences of the United States of America Medium 14769944
2013 Caspase-cleaved arrestin-2-(1-380) directly binds tBID and doubles tBid-induced cytochrome c release from isolated mitochondria; arrestin-2 pro-apoptotic action requires BID: it does not facilitate apoptosis in BID KO cells, and rescue of BID expression restores activity Co-immunoprecipitation of arrestin-2 fragment with tBID, isolated mitochondria cytochrome c release assay, BID-/- cells with reconstitution, caspase-3 activity assay Cell death and differentiation Medium 24141717
2000 In some cell types, tBID induces BAX insertion into mitochondria in vivo and in vitro; tBID relieves inhibition of the BAX transmembrane signal-anchor by the N-terminal domain; however, Bid-null MEFs support BAX insertion into mitochondria in response to TNFα or E1A without BID, demonstrating a parallel BID-independent pathway for BAX membrane insertion in which cytochrome c release is uncoupled from BAX insertion tBid reconstitution in vitro, Bid-null MEF apoptosis and BAX insertion assays, confocal BAX localization Cell death and differentiation Medium 11139284
2006 Human granzyme B efficiently cleaves human or mouse BID, but mouse granzyme B is highly resistant to cleaving BID, indicating the BID pathway is not a major primary mediator of mouse granzyme B cytotoxicity; substrate specificity differences mapped to tetrapeptide recognition Substrate specificity profiling, in vitro cleavage assay with human vs. mouse granzyme B and BID substrates The Journal of biological chemistry Medium 17179148
2004 BID cleavage at Asp60 and/or Asp75 (caspase-8/granzyme B target residues) is required for mitochondrial permeabilization and apoptosis induced by etoposide and gamma-radiation in p53-mutant T leukemic cells; this activation is independent of death receptor or mitochondrial inducer caspase activation; caspase-2 knockdown did not prevent BID activation by DNA damage Dominant-negative caspase constructs, CrmA expression, siRNA against caspase-2, BID cleavage site mapping, mitochondrial permeabilization assay The Journal of biological chemistry Medium 15117953

Source papers

Stage 0 corpus · 100 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
1998 Bid, a Bcl2 interacting protein, mediates cytochrome c release from mitochondria in response to activation of cell surface death receptors. Cell 2973 9727491
1996 BID: a novel BH3 domain-only death agonist. Genes & development 801 8918887
2005 PACS-2 controls endoplasmic reticulum-mitochondria communication and Bid-mediated apoptosis. The EMBO journal 492 15692567
2011 Caspase-8 and bid: caught in the act between death receptors and mitochondria. Biochimica et biophysica acta 404 21295084
2010 BID, BIM, and PUMA are essential for activation of the BAX- and BAK-dependent cell death program. Science (New York, N.Y.) 392 21127253
2002 BID regulation by p53 contributes to chemosensitivity. Nature cell biology 335 12402042
2008 Cysteine cathepsins trigger caspase-dependent cell death through cleavage of bid and antiapoptotic Bcl-2 homologues. The Journal of biological chemistry 317 18469004
2017 BID links ferroptosis to mitochondrial cell death pathways. Redox biology 312 28384611
2001 Phosphorylation of bid by casein kinases I and II regulates its cleavage by caspase 8. Molecular cell 294 11583622
2011 Fas death receptor signalling: roles of Bid and XIAP. Cell death and differentiation 292 21959933
2000 Signal transduction mediated by Bid, a pro-death Bcl-2 family proteins, connects the death receptor and mitochondria apoptosis pathways. Cell research 265 11032168
2000 p38 mitogen-activated protein kinase mediates bid cleavage, mitochondrial dysfunction, and caspase-3 activation during apoptosis induced by singlet oxygen but not by hydrogen peroxide. The Journal of biological chemistry 236 10837470
2008 Bid: a Bax-like BH3 protein. Oncogene 234 19641510
2002 Calpain-mediated Bid cleavage and calpain-independent Bak modulation: two separate pathways in cisplatin-induced apoptosis. Molecular and cellular biology 212 11940658
2000 Preservation of mitochondrial structure and function after Bid- or Bax-mediated cytochrome c release. The Journal of cell biology 210 10973993
2001 BID mediates neuronal cell death after oxygen/ glucose deprivation and focal cerebral ischemia. Proceedings of the National Academy of Sciences of the United States of America 207 11742085
2013 BID preferentially activates BAK while BIM preferentially activates BAX, affecting chemotherapy response. Molecular cell 201 24074954
2022 Quantitative sequencing using BID-seq uncovers abundant pseudouridines in mammalian mRNA at base resolution. Nature biotechnology 194 36302989
2005 A role for proapoptotic BID in the DNA-damage response. Cell 192 16122425
2002 The roles of Bid. Apoptosis : an international journal on programmed cell death 191 12207176
2005 Proapoptotic BID is an ATM effector in the DNA-damage response. Cell 190 16122426
2000 Bax, Bid and the permeabilization of the mitochondrial outer membrane in apoptosis. Current opinion in cell biology 182 10873816
2013 BID-induced structural changes in BAK promote apoptosis. Nature structural & molecular biology 169 23604079
2007 The BH3-only protein bid is dispensable for DNA damage- and replicative stress-induced apoptosis or cell-cycle arrest. Cell 166 17448999
2000 Bid acts on the permeability transition pore complex to induce apoptosis. Oncogene 160 11175349
2006 Bid, a BH3-only multi-functional molecule, is at the cross road of life and death. Gene 156 16446060
2003 Proapoptotic BID is required for myeloid homeostasis and tumor suppression. Genes & development 139 12533511
2008 Bid-induced release of AIF from mitochondria causes immediate neuronal cell death. Cell death and differentiation 127 18535584
2005 Humanin binds and nullifies Bid activity by blocking its activation of Bax and Bak. The Journal of biological chemistry 127 15661737
2000 Granzyme B induces BID-mediated cytochrome c release and mitochondrial permeability transition. The Journal of biological chemistry 125 11114298
2012 The ATM-BID pathway regulates quiescence and survival of haematopoietic stem cells. Nature cell biology 120 22446738
2011 BID regulates AIF-mediated caspase-independent necroptosis by promoting BAX activation. Cell death and differentiation 117 21738214
2002 Dynamics of expression of apoptosis-regulatory proteins Bid, Bcl-2, Bcl-X, Bax and Bak during development of murine nervous system. Cell death and differentiation 116 11840165
2016 Cleavage by Caspase 8 and Mitochondrial Membrane Association Activate the BH3-only Protein Bid during TRAIL-induced Apoptosis. The Journal of biological chemistry 113 27053107
2004 Membrane-insertion fragments of Bcl-xL, Bax, and Bid. Biochemistry 113 15323553
2004 A central role for Bid in granzyme B-induced apoptosis. The Journal of biological chemistry 107 15574417
2002 Bid-mediated mitochondrial pathway is critical to ischemic neuronal apoptosis and focal cerebral ischemia. The Journal of biological chemistry 103 12200426
2000 BID-dependent and BID-independent pathways for BAX insertion into mitochondria. Cell death and differentiation 102 11139284
2011 Non-apoptotic role of BID in inflammation and innate immunity. Nature 99 21552281
2011 Fas-mediated neutrophil apoptosis is accelerated by Bid, Bak, and Bax and inhibited by Bcl-2 and Mcl-1. Proceedings of the National Academy of Sciences of the United States of America 99 21768356
2004 Bid-dependent generation of oxygen radicals promotes death receptor activation-induced apoptosis in murine hepatocytes. Hepatology (Baltimore, Md.) 97 15368445
2020 Caspase-1 cleaves Bid to release mitochondrial SMAC and drive secondary necrosis in the absence of GSDMD. Life science alliance 96 32345661
2006 Mouse and human granzyme B have distinct tetrapeptide specificities and abilities to recruit the bid pathway. The Journal of biological chemistry 94 17179148
2006 Proapoptotic Bid is required for pulmonary fibrosis. Proceedings of the National Academy of Sciences of the United States of America 93 16537427
2000 Bid, a critical mediator for apoptosis induced by the activation of Fas/TNF-R1 death receptors in hepatocytes. Journal of molecular medicine (Berlin, Germany) 92 10933582
2002 Expression of Bcl-2 family member Bid in normal and malignant tissues. Neoplasia (New York, N.Y.) 78 11896568
2008 Proapoptotic BH3-only protein Bid is essential for death receptor-induced apoptosis of pancreatic beta-cells. Diabetes 70 18252892
2001 The bile acid-activated phosphatidylinositol 3-kinase pathway inhibits Fas apoptosis upstream of bid in rodent hepatocytes. Gastroenterology 70 11375961
2004 Bid truncation, bid/bax targeting to the mitochondria, and caspase activation associated with neutrophil apoptosis are inhibited by granulocyte colony-stimulating factor. Journal of immunology (Baltimore, Md. : 1950) 68 15153524
2003 BID-D59A is a potent inducer of apoptosis in primary embryonic fibroblasts. The Journal of biological chemistry 67 12519725
2002 Bid induces cytochrome c-impermeable Bax channels in liposomes. The Biochemical journal 66 11964155
2016 Bcl-2 proteins bid and bax form a network to permeabilize the mitochondria at the onset of apoptosis. Cell death & disease 59 27763642
2017 The caspase-8/Bid/cytochrome c axis links signals from death receptors to mitochondrial reactive oxygen species production. Free radical biology & medicine 57 28888620
2006 Downregulation of Bid is associated with PKCepsilon-mediated TRAIL resistance. Cell death and differentiation 52 17186022
2001 Decreased expression of Bid in human hepatocellular carcinoma is related to hepatitis B virus X protein. European journal of cancer (Oxford, England : 1990) 52 11527698
2016 DNA Damage-Induced HSPC Malfunction Depends on ROS Accumulation Downstream of IFN-1 Signaling and Bid Mobilization. Cell stem cell 50 27641306
2013 Caspase-cleaved arrestin-2 and BID cooperatively facilitate cytochrome C release and cell death. Cell death and differentiation 48 24141717
2004 Inactivating mutation of the pro-apoptotic gene BID in gastric cancer. The Journal of pathology 47 15095271
2015 Liver Bid suppression for treatment of fibrosis associated with non-alcoholic steatohepatitis. Journal of hepatology 46 26555271
2009 Execution of superoxide-induced cell death by the proapoptotic Bcl-2-related proteins Bid and Bak. Molecular and cellular biology 44 19332555
2005 Deletion of Bid impedes cell proliferation and hepatic carcinogenesis. The American journal of pathology 43 15855651
2011 Caveolin-1 mediates Fas-BID signaling in hyperoxia-induced apoptosis. Free radical biology & medicine 42 21382479
2006 Bid-independent mitochondrial activation in tumor necrosis factor alpha-induced apoptosis and liver injury. Molecular and cellular biology 39 17101783
2011 Bid and Bax are involved in granulosa cell apoptosis during follicular atresia in porcine ovaries. The Journal of reproduction and development 38 21441714
2019 HAP1 loss confers l-asparaginase resistance in ALL by downregulating the calpain-1-Bid-caspase-3/12 pathway. Blood 37 30819925
2009 Bid integrates intrinsic and extrinsic signaling in apoptosis induced by alpha-tocopheryl succinate in human gastric carcinoma cells. Cancer letters 37 19640637
2010 Bid regulates the pathogenesis of neurotropic reovirus. PLoS pathogens 36 20617182
2006 Targeting Bid to prevent programmed cell death in neurons. Biochemical Society transactions 36 17073814
2004 Requirement for aspartate-cleaved bid in apoptosis signaling by DNA-damaging anti-cancer regimens. The Journal of biological chemistry 36 15117953
2015 Activation of Fas death receptor pathway and Bid in hepatocytes is involved in saikosaponin D induction of hepatotoxicity. Environmental toxicology and pharmacology 35 26645133
2014 The expression of Bcl-2 and BID in gastric cancer cells. Journal of immunology research 35 24741635
2014 Gli1 protein regulates the S-phase checkpoint in tumor cells via Bid protein, and its inhibition sensitizes to DNA topoisomerase 1 inhibitors. The Journal of biological chemistry 35 25253693
2019 Caspase-7 mediates caspase-1-induced apoptosis independently of Bid. Microbiology and immunology 33 31687791
2015 Caspase-3 feedback loop enhances Bid-induced AIF/endoG and Bak activation in Bax and p53-independent manner. Cell death & disease 33 26469967
2006 Bax and Bid, two proapoptotic Bcl-2 family members, inhibit homologous recombination, independently of apoptosis regulation. Oncogene 33 16407825
2003 Three novel Bid proteins generated by alternative splicing of the human Bid gene. The Journal of biological chemistry 33 14583606
2014 Tax contributes apoptosis resistance to HTLV-1-infected T cells via suppression of Bid and Bim expression. Cell death & disease 32 25522269
2007 Real-time monitoring full length bid interacting with Bax during TNF-alpha-induced apoptosis. Apoptosis : an international journal on programmed cell death 32 17520191
2014 Matrine inhibits proliferation and induces apoptosis via BID-mediated mitochondrial pathway in esophageal cancer cells. Molecular biology reports 31 24510386
2010 Bid stands at the crossroad of stress-response pathways. Current cancer drug targets 31 20482490
2009 Programmed necrotic cell death induced by complement involves a Bid-dependent pathway. Journal of immunology (Baltimore, Md. : 1950) 31 19109183
2004 The promyelocytic leukemia zinc finger protein down-regulates apoptosis and expression of the proapoptotic BID protein in lymphocytes. Proceedings of the National Academy of Sciences of the United States of America 31 14769944
2021 Stepwise activation of the pro-apoptotic protein Bid at mitochondrial membranes. Cell death and differentiation 30 33462413
2002 Sequence and functional similarities between pro-apoptotic Bid and plant lipid transfer proteins. Biochimica et biophysica acta 30 11997142
2006 Acyl coenzyme A-binding protein augments bid-induced mitochondrial damage and cell death by activating mu-calpain. The Journal of biological chemistry 28 16908521
2023 BID-seq for transcriptome-wide quantitative sequencing of mRNA pseudouridine at base resolution. Nature protocols 27 37968414
2015 RIP1-dependent Bid cleavage mediates TNFα-induced but Caspase-3-independent cell death in L929 fibroblastoma cells. Apoptosis : an international journal on programmed cell death 27 25398540
2009 BH3-only protein bid participates in the Bcl-2 network in healthy liver cells. Hepatology (Baltimore, Md.) 27 19839062
2002 Temporal and spatial profile of Bid cleavage after experimental traumatic brain injury. Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism 27 12172380
2011 Stage-specific expression of TNFα regulates bad/bid-mediated apoptosis and RIP1/ROS-mediated secondary necrosis in Birnavirus-infected fish cells. PloS one 26 21304825
2010 Activity of protein kinase CK2 uncouples Bid cleavage from caspase-8 activation. Journal of cell science 26 20356928
2010 BH3-only protein Bid is dispensable for seizure-induced neuronal death and the associated nuclear accumulation of apoptosis-inducing factor. Journal of neurochemistry 26 20646170
2010 Proapoptotic Bid mediates the Atr-directed DNA damage response to replicative stress. Cell death and differentiation 26 21113148
2014 BID mediates selective killing of APC-deficient cells in intestinal tumor suppression by nonsteroidal antiinflammatory drugs. Proceedings of the National Academy of Sciences of the United States of America 25 25368155
2010 Deficiency of Bid protein reduces sepsis-induced apoptosis and inflammation, while improving septic survival. Shock (Augusta, Ga.) 25 20023601
2008 Bid is required in NPe6-PDT-induced apoptosis. Photochemistry and photobiology 25 18173728
2011 Bid and Bim collaborate during induction of T cell death in persistent infection. Journal of immunology (Baltimore, Md. : 1950) 24 21339359
2011 BID binds to replication protein A and stimulates ATR function following replicative stress. Molecular and cellular biology 24 21859891
2009 The BH3-only protein bid does not mediate death-receptor-induced liver injury in obstructive cholestasis. The American journal of pathology 24 19661444
2006 BID as a double agent in cell life and death. Cell cycle (Georgetown, Tex.) 24 16582605

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