Affinage

BIK

Bcl-2-interacting killer · UniProt Q13323

Length
160 aa
Mass
18.0 kDa
Annotated
2026-06-09
100 papers in source corpus 39 papers cited in narrative 39 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

BIK (NBK) is a BH3-only pro-apoptotic member of the BCL-2 family that initiates the intrinsic apoptotic pathway from the endoplasmic reticulum, where it resides via a C-terminal transmembrane anchor (PMID:8816500, PMID:11884414, PMID:11971188). It was originally identified by its capacity to bind anti-apoptotic proteins BCL-2, BCL-XL, and viral homologs (EBV-BHRF1, adenovirus E1B-19K) through a conserved BH3 domain, the death-promoting activity of which is neutralized by these survival proteins (PMID:7478623, PMID:8816500). Structure-function dissection established the BH3 region (residues 57–74) as the heterodimerization interface, while additional C-terminal sequences are required for efficient killing (PMID:9305912, PMID:12467227). Rather than directly engaging effectors, BIK acts largely as a 'sensitizer': it does not bind BAX directly but displaces effectors such as BAK from MCL-1 and BCL-XL sequestration, and the resulting activation of BAX or BAK depends on cellular MCL-1 levels (PMID:12853473, PMID:17403773, PMID:18025305). From its ER station, BIK drives BAX/BAK-dependent Ca2+ release from ER stores and a DRP1-dependent remodeling of mitochondrial cristae that mobilizes cytochrome c, cooperating with mitochondrial BH3 proteins like NOXA for rapid cytochrome c release (PMID:15791210, PMID:15809295); it can also relocalize to ER–mitochondria contact sites to directly bind mitochondrial BCL-XL/BCL-2 via its BH3 helix and assembles a BIK–DAPk1–ERK1/2–BAK complex that enriches ER-associated BAK and disrupts BCL-2–IP3R interaction to gate Ca2+ flux (PMID:28986568, PMID:36603764). BIK is transcriptionally induced by diverse death stimuli—via E2F and p53 during genotoxic and oncogene stress, by TGF-beta/Smad and PAR bZIP factors, and through Star-PAP-dependent 3' end processing after DNA damage (PMID:11971188, PMID:19136942, PMID:22244330, PMID:17027756, PMID:19219069). Its activity is tightly restrained post-translationally: CKIIalpha phosphorylation at Thr33/Ser35 activates BIK in a cell-cycle-restricted manner, ERK1/2 phosphorylation at Thr124 promotes Lys33 ubiquitination, and the Cul5-ASB11 E3 ligase (regulated by the IRE1alpha-XBP1s axis) targets BIK for proteasomal degradation, while GRP78/BiP sequesters BIK at the ER independent of its BH3 domain (PMID:11084041, PMID:22388352, PMID:31387940, PMID:34741311, PMID:21622563, PMID:17440086). Genetic evidence places BIK in physiological apoptosis—redundant with BIM upstream of BAX in spermatogenesis (PMID:16270031)—and in IFN-gamma-driven clearance of airway epithelium and suppression of low-grade inflammation, the latter through a non-apoptotic role modifying the BCL-2 BH4 domain to recruit proteasome subunits RPN1/RPN2 for degradation of nuclear p65 (PMID:18981230, PMID:38113109). BIK is also co-opted by viruses, being required for efficient HCV and influenza A virus replication (PMID:25463603, PMID:26437021, PMID:40627391).

Mechanistic history

Synthesis pass · year-by-year structured walk · 19 steps
  1. 1995 High

    Established BIK as a pro-apoptotic protein defined by a BH3 domain that physically engages anti-apoptotic BCL-2 family and viral survival proteins, framing it as a counter-regulator of cell survival machinery.

    Evidence Co-IP, yeast two-hybrid, and transient transfection apoptosis assays identifying BCL-2/BCL-XL/BHRF1/E1B-19K binding

    PMID:7478623 PMID:8816500

    Open questions at the time
    • Did not resolve whether BIK acts directly on effectors or only sequesters anti-apoptotic proteins
    • Subcellular site of action undefined
  2. 1997 High

    Defined the BH3 (57–74) as the heterodimerization core but showed heterodimerization alone is insufficient for killing, implicating additional C-terminal determinants and positioning BIK in the mid-stream caspase cascade.

    Evidence Deletion mutagenesis with functional apoptosis assays; CrmA/IAP epistasis

    PMID:9082997 PMID:9305912

    Open questions at the time
    • Molecular function of the C-terminal requirement not defined
    • Epistasis placement based on single-method overexpression
  3. 2000 High

    Identified BIK as a phosphoprotein whose apoptotic activity requires CKII-like phosphorylation at Thr33/Ser35, separating its killing function from its heterodimerization activity.

    Evidence Metabolic 32P labeling, phosphosite mutagenesis (T33A/S35A), partial kinase purification; genomic/promoter characterization

    PMID:10974546 PMID:11084041

    Open questions at the time
    • Kinase identity not definitively established at this stage
    • How phosphorylation activates BIK mechanistically unknown
  4. 2002 High

    Localized BIK action to the ER membrane and demonstrated it triggers mitochondrial cytochrome c release in a BH3-dependent, distance-acting manner; linked BIK induction to the E1A/p53 axis.

    Evidence Subcellular fractionation, membrane-anchor swap, in vitro reconstitution; microarray/RT-PCR for p53-dependent induction

    PMID:11884414 PMID:11971188

    Open questions at the time
    • The diffusible signal from ER to mitochondria not identified
    • Effector dependency (BAX vs BAK) not resolved
  5. 2003 High

    Showed BIK acts as a sensitizer requiring BAX—not directly binding it but driving its conformational activation—and confirmed BH3-dependent antitumor activity in vivo.

    Evidence BAX-KO/reconstitution, conformational antibody and cytochrome c assays, Co-IP; xenograft with BH3 deletion mutant

    PMID:12467227 PMID:12853473

    Open questions at the time
    • Why BAK is dispensable in these settings unresolved
    • Identity of the effector-activating intermediary unknown
  6. 2005 High

    Resolved the ER-to-mitochondria mechanism: BIK drives BAX/BAK-dependent ER Ca2+ release and a DRP1-dependent cristae remodeling that mobilizes cytochrome c, cooperating with NOXA for rapid release.

    Evidence Live-cell imaging, BAX/BAK DKO cells, dominant-negative/siRNA DRP1, Ca2+ imaging, selective permeabilization

    PMID:15791210 PMID:15809295

    Open questions at the time
    • How DRP1-independent cristae opening is mechanically achieved unclear
    • Direct molecular link between Ca2+ release and effector activation incomplete
  7. 2005 High

    Demonstrated BIK is constitutively degraded by the proteasome and that proteasome inhibition (bortezomib) requires BIK for cytotoxicity, establishing protein stability as a key activity switch.

    Evidence BIK/BIM double-KO MEFs, RNAi, Western blot, cell death assays; in vivo spermatogenesis double-KO genetics

    PMID:15767553 PMID:16270031

    Open questions at the time
    • E3 ligase responsible not yet identified
    • Functional redundancy with BIM limits single-gene phenotype interpretation
  8. 2007 High

    Defined how anti-apoptotic context dictates effector choice: BIK displaces BAK from MCL-1/BCL-XL, and MCL-1 levels determine whether BIK kills via BAX or BAK, particularly in response to translation shutoff.

    Evidence Genetic KO/reconstitution, displacement Co-IP, MCL-1 siRNA, BAX/BAK-deficient cells

    PMID:17403773 PMID:18025305

    Open questions at the time
    • Quantitative affinity hierarchy of BIK for different anti-apoptotic proteins not measured
    • Stimulus specificity for translation inhibition mechanistically incomplete
  9. 2007 High

    Identified GRP78/BiP as a BH3-independent ER inhibitor of BIK and revealed a caspase-independent autophagic death program activated by BIK in BCL-2-null cells.

    Evidence Reciprocal Co-IP, domain mapping, siRNA rescue; BCL-2 KO MEFs with PI3K/ATG5/Beclin-1 interventions and EM

    PMID:17440086 PMID:17873911

    Open questions at the time
    • Mechanism linking BIK to autophagy machinery undefined
    • Autophagic-death finding is Medium confidence, single lab
  10. 2008 High

    Uncovered post-translational and proteolytic regulation: RHBDD1 cleaves BIK within its TM region, and BIK suppresses nuclear translocation of phospho-ERK1/2 to drive IFN-gamma-induced epithelial death in vivo.

    Evidence RHBDD1 catalytic-residue mutagenesis and KD/OE; Bik-KO mice, BikL61G mutant, Co-IP, immunofluorescence, allergen model

    PMID:18953687 PMID:18981230

    Open questions at the time
    • RHBDD1 cleavage finding Medium confidence, single lab
    • How a membrane-anchored BIK influences nuclear ERK trafficking is mechanistically unclear
  11. 2009 Medium

    Mapped transcriptional control of BIK to stimulus-specific factors: TGF-beta/Smad directly induces BIK while repressing BCL-XL, and PAR bZIP factors mediate oxidative-stress-induced apoptosis through BIK.

    Evidence ChIP, promoter reporters, shRNA/siRNA rescue; PAR bZIP triple-KO fibroblasts

    PMID:19136942 PMID:19219069

    Open questions at the time
    • Integration of multiple transcriptional inputs not reconciled
    • PAR bZIP work single lab, Medium confidence
  12. 2012 High

    Revealed two distinct regulatory layers: Star-PAP/PKCdelta/PIPKIalpha controls BIK mRNA 3' processing after DNA damage, and Src-Ras-ERK1/2 phosphorylation of Thr124 drives Lys33 ubiquitylation and degradation downstream of oncogenic signaling.

    Evidence siRNA, Co-IP, kinase and 3'-processing assays; phospho/ubiquitin site mapping in v-Src fibroblasts with proteasome and ERK inhibitors

    PMID:22244330 PMID:22388352

    Open questions at the time
    • E3 ligase acting downstream of Thr124 phosphorylation not identified here
    • Cross-talk between transcriptional and degradative control undefined
  13. 2014 Medium

    Linked autophagy and an alternative GRP78 mechanism to BIK levels: SQSTM1/p62-mediated autophagy clears ER-associated BIK, and GRP78 competes with BCL-2 for BIK to confer endocrine resistance.

    Evidence shRNA, Co-IP, autophagy inhibitors, xenograft; competitive Co-IP with BH3-deletion mutants

    PMID:21622563 PMID:25002530

    Open questions at the time
    • Relative contributions of autophagic vs proteasomal turnover not quantified
    • p62 finding Medium confidence, single lab
  14. 2017 High

    Built a spatial model of BIK action at ER–mitochondria junctions: BIK assembles a BIK–DAPk1–ERK1/2–BAK complex, enriches ER-associated BAK, disrupts BCL-2–IP3R to release ER Ca2+, and connects p53 suppression of BiP to BIK release during ER stress.

    Evidence Co-IP, domain mapping, Ca2+ imaging, contact-site quantification, BIK peptides, allergen model; BiP mRNA binding/reporter assays for p53

    PMID:28622297 PMID:28986568

    Open questions at the time
    • Stoichiometry and assembly order of the BIK–DAPk1–BAK complex undefined
    • p53/BiP arm is Medium confidence
  15. 2019 High

    Identified Cul5-ASB11 as the E3 ligase for BIK and integrated it into the ER-stress response: IRE1alpha-XBP1s activates ASB11 to degrade BIK during adaptive survival, while genotoxic stress downregulates this axis to stabilize BIK.

    Evidence Co-IP, ubiquitination assays, ASB11/IRE1alpha manipulation, XBP1s overexpression, in vivo tumor model

    PMID:31387940

    Open questions at the time
    • How ASB11 substrate recognition is regulated unknown
    • Relationship to Thr124-phosphorylation degradation pathway not reconciled
  16. 2021 High

    Identified CKIIalpha as the activating kinase for BIK Thr33/Ser35 and showed its G2/M-restricted expression renders BIK a selective killer of proliferating cells.

    Evidence FUCCI cell-cycle tracking, proteomics/Co-IP, phosphosite mutagenesis, CKIIalpha siRNA, airway cells and mouse model

    PMID:34741311

    Open questions at the time
    • Structural basis for phospho-activation not solved
    • Interplay with degradative phosphorylation events undefined
  17. 2023 High

    Established direct BIK–anti-apoptotic binding at mitochondria/ER-mitochondria contacts and uncovered a non-apoptotic role in which BIK directs BCL-2 BH4-mediated proteasomal degradation of nuclear p65 to suppress inflammation.

    Evidence FLIM-FRET, BH3 mutagenesis, BAX/BAK DKO and mito-targeted BCL-XL chimeras; Bik KO/transgenic mice, BIK-BCL-2/RPN1/RPN2 Co-IP, fractionation

    PMID:36603764 PMID:38113109

    Open questions at the time
    • How BIK toggles between pro-apoptotic and proteasome-recruiting modes unclear
    • Basis of sex-specific BIK/BCL-2 expression not fully explained
  18. 2023 High

    Connected BIK to ER-membrane sensing complexes, showing TMEM215-GRP78-BIK assemblies gate endothelial apoptosis via MAM Ca2+ flux through IP3R and MCU.

    Evidence Co-IP-MS, siRNA with BIK rescue, Ca2+ imaging, IP3R/MCU inhibitors, EC-specific Tmem215 KO mouse

    PMID:37750320

    Open questions at the time
    • How TMEM215 loss liberates BIK from GRP78 mechanistically undefined
    • Tissue specificity of this complex unexplored
  19. 2025 High

    Defined a viral exploitation axis: influenza A and HCV co-opt BIK for replication, with IAV NP suppressing the proteasome to accumulate BIK and disrupting BCL-2/NP interactions, and a BIK promoter SNP correlating with influenza severity.

    Evidence Co-IP (BIK-NP, BCL-2-NP), proteasome subunit manipulation, BIK KO/transgenic mice, primary cultures, human cohort genotyping; earlier HCV NS5B and IAV NP/M2 cleavage studies

    PMID:25463603 PMID:26437021 PMID:40627391

    Open questions at the time
    • Mechanism by which a pro-apoptotic protein aids viral replication not fully resolved
    • HCV interaction is Medium confidence

Open questions

Synthesis pass · forward-looking unresolved questions
  • How BIK's molecular state is switched between its canonical pro-apoptotic effector-sensitizing function and its non-apoptotic proteasome-directing role, and how the competing activating phosphorylation, degradative phosphorylation/ubiquitination, and chaperone-sequestration inputs are integrated to set a death threshold, remains unresolved.
  • No structural model of activated BIK at ER-mitochondria contacts
  • Quantitative integration of opposing regulatory inputs not established
  • Mechanistic basis for BIK promoting viral replication unresolved

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0098772 molecular function regulator activity 5 GO:0140313 molecular sequestering activity 3
Localization
GO:0005783 endoplasmic reticulum 4 GO:0005739 mitochondrion 1
Pathway
R-HSA-5357801 Programmed Cell Death 5 R-HSA-8953897 Cellular responses to stimuli 3
Partners
ASB11BAK1BCL2BCL2L1DAPK1HSPA5MCL1TMEM215
Complex memberships
BIK-DAPk1-ERK1/2-BAK complexTMEM215-GRP78-BIK complex

Evidence

Reading pass · 39 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
1995 BIK was identified as a novel pro-apoptotic protein that interacts with anti-apoptotic proteins BCL-2, BCL-XL, EBV-BHRF1, and adenovirus E1B-19K via a conserved 9 amino acid BH3 domain. Death-promoting activity of BIK can be suppressed by co-expression of these survival proteins. Co-immunoprecipitation, yeast two-hybrid, transient transfection apoptosis assays Oncogene High 7478623
1996 NBK/BIK was cloned from a yeast two-hybrid screen for proteins interacting with E1B 19K. It contains only BH3 (not BH1/BH2), interacts with BCL-2 and E1B 19K in vitro, co-localizes with cytoplasmic and nuclear membranes, antagonizes 19K-mediated inhibition of apoptosis, and induces apoptosis independently of BAX. Yeast two-hybrid, in vitro binding, transient transfection, co-localization, functional apoptosis assays Molecular and cellular biology High 8816500
1997 Functional dissection showed that the BH3 domain of BIK (residues 57-74) is the core heterodimerization domain for BCL-2 and BCL-XL, but heterodimerization alone is insufficient for cell death; additional C-terminal sequences (residues 120-134 beyond the BH3) are required for efficient apoptotic activity. Deletion mutagenesis, yeast two-hybrid, co-immunoprecipitation, functional apoptosis assays in mammalian cells The Journal of biological chemistry High 9305912
1997 BIK and BAK engage the apoptotic death pathway downstream of the CrmA block but upstream of the IAP (inhibitor of apoptosis) block, positioning them in the mid-stream of caspase activation cascade. Genetic epistasis using CrmA and IAP overexpression combined with BIK/BAK transfection and cell death assays The Journal of biological chemistry Medium 9082997
2000 BIK is a phosphoprotein phosphorylated at threonine 33 and serine 35. Mutation of these phosphorylation sites (T33A/S35A) reduces apoptotic activity without significantly affecting heterodimerization with BCL-2, indicating phosphorylation is required for efficient apoptotic function. Partial purification of kinase activity from HeLa cell cytoplasm suggests a casein kinase II-related enzyme phosphorylates BIK. Metabolic 32P labeling, site-directed mutagenesis, kinase assays, functional apoptosis assays The Journal of biological chemistry High 11084041
2000 The human BIK gene is located at chromosome 22q13.3, spans ~19 kb, comprises 5 exons, and is expressed ubiquitously with elevated levels in heart and skeletal muscle. A minimal promoter was localized to -211 to +153 lacking TATA/CAAT boxes. FISH, genomic cloning, Northern blot, promoter-reporter transfection, deletion mutagenesis Gene Medium 10974546
2002 BIK is an ER-resident protein (containing a C-terminal transmembrane segment) that stimulates cytochrome c release from mitochondria. A BH3-domain-dependent mechanism is required. Restricting BIK to the ER membrane with a cytochrome b5 anchor retains its cytochrome c release activity. ER BIK activity requires ER/light membrane fractions and cytosol in an in vitro reconstitution assay. Subcellular fractionation, membrane anchor replacement, in vitro reconstitution, cytochrome c release assay, BH3 mutagenesis The Journal of biological chemistry High 11884414
2002 BIK/NBK is transcriptionally induced downstream of E1A in a p53-dependent manner. BIK induces caspase-dependent cell death in p53-null cells. A BH3 point mutation abrogates BIK function. Endogenous and ectopic BIK associates with the endoplasmic reticulum. DNA microarray, RT-PCR, Western blot, subcellular fractionation, BH3 domain mutagenesis, apoptosis assays Oncogene High 11971188
2003 NBK/BIK-induced apoptosis requires BAX but not BAK; BIK expression causes a conformational switch in BAX N-terminus, cytochrome c release, and mitochondrial permeability transition. Immunoprecipitation shows BIK interacts with BCL-XL and BCL-2 but NOT with BAX directly. BIK does not localize to mitochondria, suggesting it acts indirectly as a 'sensitizer' to trigger BAX-dependent apoptosis. Adenoviral tetracycline-regulated expression, BAX-knockout/reconstitution, immunoprecipitation, co-immunoprecipitation, conformational antibody assay, cytochrome c release assay The EMBO journal High 12853473
2005 ER-localized BIK activates a DRP1-dependent pathway that causes mitochondrial fragmentation and remodeling/opening of cristae (mobilizing intramitochondrial cytochrome c stores), distinct from DRP1's role in mitochondrial fission. BIK cooperates with the mitochondria-targeted BH3-only protein NOXA to activate BAX, causing rapid cytochrome c release and caspase activation, by a mechanism independent of DRP1 enzyme activity. Live cell imaging, selective digitonin permeabilization, dominant-negative DRP1, siRNA knockdown, co-expression experiments, cytochrome c localization The EMBO journal High 15791210
2005 ER-localized BIK regulates BAX/BAK-dependent Ca2+ release from ER stores upstream of effector caspase activation. BIK-induced Ca2+ release is abolished in BAX/BAK double-deficient cells but restored by ectopic BAK. p53 stimulates BAK recruitment to the ER, which is inhibited by BIK siRNA. DRP1 (Ca2+-regulated GTPase) is involved in p53-induced mitochondrial fission and cytochrome c release. siRNA knockdown, BAX/BAK double-KO cells, intracellular Ca2+ measurements, subcellular fractionation, dominant-negative constructs The Journal of biological chemistry High 15809295
2005 Bortezomib stabilizes BIK protein from proteasomal degradation, leading to BIK accumulation that mediates apoptosis. BIK (and BIM) are required for bortezomib cytotoxicity; double-KO MEFs or cells with RNAi-mediated knockdown of both BIK and BIM are refractory to bortezomib. This establishes that BIK is normally degraded by the proteasome. Mouse embryo fibroblast double-KO, RNAi knockdown, Western blot, cell death assays Molecular cancer therapeutics High 15767553
2007 NBK/BIK activates BAK-dependent apoptosis in response to protein synthesis inhibition by antagonizing/displacing BAK from MCL-1 and BCL-XL sequestration. NBK/BIK-deficient and BAK-deficient cells are resistant to MazF toxin and pharmacologic translation inhibition. NBK/BIK functions as the apical regulator of a BAK-dependent apoptotic pathway specifically in response to shutoff of protein synthesis. Genetic KO cells, reconstitution, co-immunoprecipitation (displacement of BAK from MCL-1/BCL-XL), adenoviral inducible expression, pharmacological inhibitors Genes & development High 17403773
2007 GRP78/BiP forms a complex with BIK at the ER. GRP78 overexpression decreases apoptosis induced by ER-targeted BIK and inhibits estrogen starvation-induced BAX activation and mitochondrial permeability transition. GRP78 interaction with BIK does not require the BH3 domain of BIK. Co-immunoprecipitation, siRNA knockdown, overexpression, apoptosis assays, domain deletion analysis Cancer research High 17440086
2007 BCL-2-null cells expressing BIK undergo caspase-independent cell death with autophagic features (cytosolic vacuoles, LC3 puncta, Beclin-1 upregulation, AIF nuclear redistribution) without cytochrome c release. This autophagic death is blocked by PI3K inhibitors (3-MA, wortmannin) or depletion of ATG5/Beclin-1. BCL-2 KO vs. WT MEFs, BIK overexpression, caspase inhibition, PI3K inhibitors, ATG5/Beclin-1 siRNA, electron microscopy, LC3 localization Oncogene Medium 17873911
2007 MCL-1 determines the BAX dependency of NBK/BIK-induced apoptosis. MCL-1 binding to BAK persists after NBK expression and prevents BAK activation in BAX-deficient cells. Targeted knockdown of MCL-1 allows BAK activation by NBK/BIK. In contrast, PUMA can disrupt MCL-1-BAK interaction and activate both BAX and BAK. siRNA knockdown of MCL-1, co-immunoprecipitation (MCL-1-BAK interaction), BAX/BAK-deficient cells, inducible BIK/NBK expression The Journal of cell biology High 18025305
2008 BIK inhibits nuclear translocation of phospho-ERK1/2 to mediate IFN-gamma-induced cell death in airway epithelial cells. BIK (but not BikL61G mutant) physically interacts with and suppresses nuclear translocation of phospho-ERK1/2. Loss of BIK suppresses IFN-gamma-induced death and leads to persistence of hyperplastic epithelial cells. Bik KO mice, overexpression, BikL61G mutant, co-immunoprecipitation, immunofluorescence (phospho-ERK1/2 nuclear localization), in vivo allergen model The Journal of cell biology High 18981230
2008 RHBDD1, a rhomboid family serine protease, cleaves BIK at a site within its transmembrane region. RHBDD1 residues G142 and S144 are essential for this proteolytic activity. RHBDD1 overexpression reduces BIK-mediated apoptosis; RHBDD1 knockdown enhances it. This cleavage is upstream of BIK protein degradation. Site-directed mutagenesis of RHBDD1, overexpression and siRNA knockdown, Western blot for BIK cleavage, apoptosis assays Cellular and molecular life sciences Medium 18953687
2009 TGF-beta induces BIK transcription in human B cells via direct Smad binding to a consensus Smad-binding element in the BIK promoter, and simultaneously represses BCL-XL. BIK induction is required for TGF-beta-induced apoptosis; shRNA suppression of BIK diminishes it. Chromatin immunoprecipitation (ChIP) for Smad binding at BIK promoter, promoter reporter assay, shRNA knockdown, overexpression Cell death and differentiation High 19136942
2011 GRP78 forms a complex with BIK independent of the BH3 domain and competes with BCL-2 for BIK binding. Increased GRP78 expression decreases BIK-BCL-2 complex formation, thereby releasing BCL-2 from BIK sequestration. This mechanism confers endocrine resistance in breast cancer cells. Co-immunoprecipitation, BH3 deletion mutants, overexpression/knockdown, apoptosis assays The Journal of biological chemistry High 21622563
2012 BIK mRNA 3' end processing and expression are controlled by the nuclear poly(A) polymerase Star-PAP downstream of DNA damage signals. PKCdelta associates with the Star-PAP complex and is required for BIK expression. PIPKIalpha generates PI4,5P2 that directly stimulates PKCdelta activity in the Star-PAP complex. Features in the BIK 3' UTR define Star-PAP specificity and may block canonical PAP activity. siRNA/shRNA knockdown, co-immunoprecipitation, kinase assays, 3' end processing assays, reporter assays Molecular cell High 22244330
2012 Src tyrosine kinase inhibits apoptosis by increasing BIK degradation via activation of the Ras-Raf-MEK1/2-ERK1/2 pathway. ERK1/2 phosphorylates BIK on Thr124, which drives BIK ubiquitylation on Lys33 and subsequent proteasomal degradation. Phosphorylation site mapping by mutagenesis, ubiquitylation assays, proteasome inhibitor, ERK1/2 pathway inhibitors, v-Src transformed fibroblasts Cell death and differentiation High 22388352
2014 Disruption of SQSTM1/p62 causes cargo loading failure and accumulation of NBK/Bik on ER membranes (by blocking autophagic degradation of NBK/Bik), leading to apoptosis. NBK/Bik knockdown markedly attenuates apoptosis caused by SQSTM1/p62 targeting. Autophagy initiation inhibitors (Ulk1, Beclin-1, Atg5 shRNA) substantially diminish NBK/Bik accumulation, while distal autophagy blockade enhances it. shRNA knockdown, co-immunoprecipitation, Western blot for ER-associated BIK, genetic/pharmacologic autophagy inhibition, in vivo xenograft Molecular and cellular biology Medium 25002530
2017 BIK dissociates the BAK/BCL-2 complex to enrich for ER-associated BAK and interacts with the kinase domain of DAPk1, forming a BIK-DAPk1-ERK1/2-BAK complex. BIK disrupts the BCL-2-IP3R interaction to cause ER Ca2+ release. ER-associated BAK (enriched by BIK) interacts with DAPk1 calmodulin domain to increase ER-mitochondria contact sites and facilitate mitochondrial Ca2+ uptake. The BIK BH3 helix is sufficient for ER-BAK enrichment and ER Ca2+ release, but mitochondrial Ca2+ uptake also requires BAK. Co-immunoprecipitation, siRNA knockdown, domain deletion analysis, Ca2+ imaging, ER-mitochondria contact site quantification, BIK peptide experiments, mouse allergen model Nature communications High 28986568
2017 p53 promotes apoptosis during prolonged ER stress by suppressing BiP/GRP78 expression via binding to the first 346-nt of the bip mRNA through a trans-suppression domain in the first 7 N-terminal amino acids of p53ΔN40. BiP suppression releases pro-apoptotic BIK from BiP, activating apoptosis. BiP mRNA binding assays, reporter assays, p53 isoform overexpression, siRNA knockdown, apoptosis assays Cell death and differentiation Medium 28622297
2019 Cul5-ASB11 is the E3 ubiquitin ligase that targets BIK for ubiquitination and proteasomal degradation. During ER stress, XBP1s (activated by IRE1alpha) activates ASB11, which stimulates BIK ubiquitination, interaction with p97/VCP, and proteolysis, promoting cell survival during the adaptive phase. Genotoxic agents downregulate the IRE1alpha-XBP1s-ASB11 axis to stabilize BIK and promote apoptosis. Co-immunoprecipitation, ubiquitination assays, ASB11 siRNA/overexpression, IRE1alpha inhibitor, XBP1s overexpression, in vivo tumor model The Journal of cell biology High 31387940
2021 Casein kinase IIalpha (CKIIalpha) is responsible for phosphorylating BIK at Thr33/Ser35 to activate it. CKIIalpha is expressed only during G2/M phase, causing BIK to selectively kill proliferating (S/G2/M) cells. BIK phosphorylation mutants at Thr33 or Ser35 demonstrated that phosphorylation activates BIK to induce death even in quiescent cells. BIK protein is detectable only in green (S/G2/M) cells using fluorescent ubiquitin cell cycle indicators. Fluorescent ubiquitin cell cycle indicators (FUCCI), co-immunoprecipitation, proteomics, phosphorylation site mutagenesis, CKIIalpha siRNA, airway epithelial cell cultures and mouse model Journal of cellular physiology High 34741311
2023 BIK, although predominantly ER-localized, can directly bind mitochondria-localized BCL-XL and BCL-2 via its BH3 region (detected by FLIM-FRET). In BMK-BAX/BAK DKO cells, a fraction of BIK moves toward mitochondria in response to mitochondria-localized BCL-XL. In MCF-7 cells, BIK is also present at mitochondria-associated ER membranes and binds mitochondria-localized BCL-XL via relocalization. This suggests BIK initiates mitochondrial outer membrane permeabilization via direct interactions at ER-mitochondria contact sites. FLIM-FRET microscopy, BH3 mutagenesis, BAX/BAK DKO cells, mitochondria-targeted BCL-XL chimeric mutants, subcellular localization imaging The Journal of biological chemistry High 36603764
2023 BIK deficiency causes low-grade inflammation and spontaneous emphysema in female but not male mice. Mechanistically, BIK modifies the BH4 domain of BCL-2 to interact with proteasome regulatory particles RPN1 and RPN2, enhancing proteasomal degradation of nuclear proteins (including nuclear p65). BCL-2 and BIK levels are lower in female vs. male mouse lung, explaining the sex-specific phenotype. Bik KO mouse model, transgenic airway BIK overexpression, co-immunoprecipitation (BIK-BCL-2, BIK-RPN1/RPN2), proteasomal degradation assays, nuclear/cytosolic fractionation, LPS/allergen models The Journal of clinical investigation High 38113109
2023 TMEM215 forms a complex with BiP/GRP78, which in turn interacts with BIK. TMEM215 knockdown triggers BIK-dependent apoptosis in endothelial cells via increased mitochondria-associated ER membrane contacts and mitochondrial Ca2+ influx through IP3R and MCU. Inhibiting IP3R or MCU abrogates TMEM215 knockdown-induced apoptosis. Co-immunoprecipitation-mass spectrometry, siRNA knockdown, BIK siRNA rescue, Ca2+ imaging, IP3R/MCU inhibitors, EC-specific Tmem215 KO mouse Circulation research High 37750320
2014 HCV NS5B RNA polymerase induces BIK expression and co-localizes and interacts with BIK by co-immunoprecipitation, suggesting BIK interacts with the HCV replication complex. BIK is required for efficient HCV RNA replication and viral release; BIK-depleted cells show significantly reduced viral replication. Co-immunoprecipitation, immunofluorescence co-localization, siRNA knockdown, viral titer assays, BIK overexpression Virology Medium 25463603
2016 BIK mediates caspase-dependent cleavage of influenza A virus (IAV) nucleoprotein (NP) and M2 proteins, and enables cytoplasmic export of viral ribonucleoprotein. Bik-deficient mouse AECs show attenuated IAV replication, reduced caspase-3 activation, and impaired viral NP/M2 cleavage. Bik-deficient mice are protected from IAV lethality. Bik KO mouse model, siRNA knockdown in human AECs, viral titer assays, Western blot for viral protein cleavage, caspase-3 activation, viral RNP nuclear export assays American journal of respiratory cell and molecular biology High 26437021
2025 IAV nucleoprotein (NP) suppresses the β5 subunit of the proteasome, leading to BIK accumulation and enhanced viral replication. BIK interacts with NP, disrupting the BCL-2/NP interaction and promoting viral replication. β5 treatment dampens BIK levels and protects mice from IAV-induced morbidity. A BIK promoter SNP (rs738276) influences BIK expression and correlates with influenza severity. Co-immunoprecipitation (BIK-NP, BCL-2-NP), β5 subunit knockdown/treatment, BIK KO/overexpression mouse model, air-liquid interface primary cell cultures, human cohort genotyping Proceedings of the National Academy of Sciences High 40627391
2017 TMEM74, a lysosome transmembrane protein, interacts with BIK via its transmembrane (TM) domains and the BH3 domain of BIK. TMEM74 co-localizes with BIK in subcellular organelles and inhibits BIK-induced apoptosis. TM domain-deficient TMEM74 mutant loses this inhibitory function. Co-immunoprecipitation, fluorescent co-localization, domain deletion analysis, apoptosis assays, knockdown Cellular signalling Medium 28412412
2006 BIK mRNA levels are induced by fulvestrant via a p53-dependent but non-transcriptional mechanism (p53 transcriptional activity is not required, unlike for PUMA induction by doxorubicin). BIK protein is subject to rapid proteasomal degradation in some breast cancer cell lines. siRNA knockdown of p53, dominant-negative p53, reporter assay, BIK mRNA stability assay, proteasome inhibitor MG132, Western blot Cancer research Medium 17047080
2006 E2F transcription factors directly activate the BIK promoter, contributing to chemotherapy-induced BIK expression in cancer cells by a p53-independent mechanism. E2F-mediated BIK induction is required for efficient adriamycin-induced apoptosis. Promoter-reporter assays, ChIP, E2F overexpression and knockdown, apoptosis assays FEBS letters Medium 17027756
2009 PAR bZIP transcription factors (TEF, DBP) directly activate the BIK promoter. In PAR bZIP triple-KO fibroblasts, bik is the only BH3-only gene downregulated. PAR bZIP proteins mediate oxidative stress (H2O2)-induced apoptosis through BIK, as confirmed by BIK knockdown rescue experiments. PAR bZIP triple-KO mouse fibroblasts, promoter-reporter assay, ChIP, BIK siRNA rescue, oxidative stress apoptosis assays Cell death and differentiation Medium 19219069
2003 BIK antitumor activity in vivo requires an intact BH3 domain. BH3 domain deletion abolishes cytochrome c release, caspase (9, 7, 3) activation, and tumor growth suppression in xenograft models. Adenoviral overexpression, BH3 deletion mutant, cytochrome c release assay, caspase activity, nude mouse xenograft Molecular cancer therapeutics Medium 12467227
2005 Bik and Bim show functional redundancy in eliminating supernumerary spermatogonia and spermatocytes during the first wave of spermatogenesis. Bik single-KO mice are fertile, but bik-/-bim-/- double-KO adult males are infertile with arrested spermatogenesis and increased early germ cells—a phenotype similar to Bax deficiency, placing Bik and Bim upstream of Bax. Bik-KO, Bim-KO, and Bik/Bim double-KO mouse generation, histology, fertility assays The EMBO journal High 16270031

Source papers

Stage 0 corpus · 100 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
1995 Bik, a novel death-inducing protein shares a distinct sequence motif with Bcl-2 family proteins and interacts with viral and cellular survival-promoting proteins. Oncogene 408 7478623
2005 Endoplasmic reticulum BIK initiates DRP1-regulated remodelling of mitochondrial cristae during apoptosis. The EMBO journal 284 15791210
2007 GRP78/BiP inhibits endoplasmic reticulum BIK and protects human breast cancer cells against estrogen starvation-induced apoptosis. Cancer research 264 17440086
1996 Induction of apoptosis by human Nbk/Bik, a BH3-containing protein that interacts with E1B 19K. Molecular and cellular biology 168 8816500
2005 The proteasome inhibitor bortezomib sensitizes cells to killing by death receptor ligand TRAIL via BH3-only proteins Bik and Bim. Molecular cancer therapeutics 150 15767553
2005 BH3-only BIK regulates BAX,BAK-dependent release of Ca2+ from endoplasmic reticulum stores and mitochondrial apoptosis during stress-induced cell death. The Journal of biological chemistry 149 15809295
2016 LncRNA H19 confers chemoresistance in ERα-positive breast cancer through epigenetic silencing of the pro-apoptotic gene BIK. Oncotarget 125 27845892
2002 BH-3-only BIK functions at the endoplasmic reticulum to stimulate cytochrome c release from mitochondria. The Journal of biological chemistry 123 11884414
2011 Novel mechanism of anti-apoptotic function of 78-kDa glucose-regulated protein (GRP78): endocrine resistance factor in breast cancer, through release of B-cell lymphoma 2 (BCL-2) from BCL-2-interacting killer (BIK). The Journal of biological chemistry 113 21622563
2007 NBK/BIK antagonizes MCL-1 and BCL-XL and activates BAK-mediated apoptosis in response to protein synthesis inhibition. Genes & development 113 17403773
2005 Bik/NBK accumulation correlates with apoptosis-induction by bortezomib (PS-341, Velcade) and other proteasome inhibitors. Oncogene 109 15824729
2003 Induction of cell death by the BH3-only Bcl-2 homolog Nbk/Bik is mediated by an entirely Bax-dependent mitochondrial pathway. The EMBO journal 107 12853473
2002 Induction and endoplasmic reticulum location of BIK/NBK in response to apoptotic signaling by E1A and p53. Oncogene 107 11971188
2008 BIK, the founding member of the BH3-only family proteins: mechanisms of cell death and role in cancer and pathogenic processes. Oncogene 103 19641504
2004 Proapoptotic BH3-only Bcl-2 family member Bik/Blk/Nbk is expressed in hemopoietic and endothelial cells but is redundant for their programmed death. Molecular and cellular biology 99 14749373
2006 Loss of the tissue-specific proapoptotic BH3-only protein Nbk/Bik is a unifying feature of renal cell carcinoma. Cell death and differentiation 86 16322756
2005 Concomitant loss of proapoptotic BH3-only Bcl-2 antagonists Bik and Bim arrests spermatogenesis. The EMBO journal 85 16270031
2009 TGF-beta induces apoptosis in human B cells by transcriptional regulation of BIK and BCL-XL. Cell death and differentiation 77 19136942
2000 Phosphorylation of the pro-apoptotic protein BIK: mapping of phosphorylation sites and effect on apoptosis. The Journal of biological chemistry 74 11084041
2004 The Bik BH3-only protein is induced in estrogen-starved and antiestrogen-exposed breast cancer cells and provokes apoptosis. Proceedings of the National Academy of Sciences of the United States of America 72 14983013
2014 Targeting SQSTM1/p62 induces cargo loading failure and converts autophagy to apoptosis via NBK/Bik. Molecular and cellular biology 68 25002530
2012 Star-PAP control of BIK expression and apoptosis is regulated by nuclear PIPKIα and PKCδ signaling. Molecular cell 68 22244330
2002 Systemic tumor suppression by the proapoptotic gene bik. Cancer research 65 11782349
2008 Bortezomib induces apoptosis via Bim and Bik up-regulation and synergizes with cisplatin in the killing of head and neck squamous cell carcinoma cells. Molecular cancer therapeutics 62 18566236
2007 BH3-only protein BIK induces caspase-independent cell death with autophagic features in Bcl-2 null cells. Oncogene 57 17873911
1997 Functional dissection of the pro-apoptotic protein Bik. Heterodimerization with anti-apoptosis proteins is insufficient for induction of cell death. The Journal of biological chemistry 54 9305912
2005 Proteasome inhibitors-mediated TRAIL resensitization and Bik accumulation. Cancer biology & therapy 53 16082182
1997 Bik and Bak induce apoptosis downstream of CrmA but upstream of inhibitor of apoptosis. The Journal of biological chemistry 51 9082997
2002 The apoptosis promoting Bcl-2 homologues Bak and Nbk/Bik overcome drug resistance in Mdr-1-negative and Mdr-1-overexpressing breast cancer cell lines. Oncogene 50 11803466
2018 KLF4, a miR-32-5p targeted gene, promotes cisplatin-induced apoptosis by upregulating BIK expression in prostate cancer. Cell communication and signaling : CCS 49 30176890
2012 Src tyrosine kinase inhibits apoptosis through the Erk1/2- dependent degradation of the death accelerator Bik. Cell death and differentiation 49 22388352
2008 A novel member of the Rhomboid family, RHBDD1, regulates BIK-mediated apoptosis. Cellular and molecular life sciences : CMLS 49 18953687
2017 p53-mediated suppression of BiP triggers BIK-induced apoptosis during prolonged endoplasmic reticulum stress. Cell death and differentiation 48 28622297
2006 Regulation of expression of BIK proapoptotic protein in human breast cancer cells: p53-dependent induction of BIK mRNA by fulvestrant and proteasomal degradation of BIK protein. Cancer research 48 17047080
2008 The BH3-only protein Bik/Blk/Nbk inhibits nuclear translocation of activated ERK1/2 to mediate IFNgamma-induced cell death. The Journal of cell biology 46 18981230
2003 Enhancement of Bik antitumor effect by Bik mutants. Cancer research 45 14633680
2011 Cigarette smoke suppresses Bik to cause epithelial cell hyperplasia and mucous cell metaplasia. American journal of respiratory and critical care medicine 44 21317312
2003 Mutations of the BIK gene in human peripheral B-cell lymphomas. Genes, chromosomes & cancer 44 12874789
2007 Mcl-1 determines the Bax dependency of Nbk/Bik-induced apoptosis. The Journal of cell biology 43 18025305
1999 Expression of the death gene Bik/Nbk promotes sensitivity to drug-induced apoptosis in corticosteroid-resistant T-cell lymphoma and prevents tumor growth in severe combined immunodeficient mice. Blood 43 10419903
2001 Involvement of Bik, a proapoptotic member of the Bcl-2 family, in surface IgM-mediated B cell apoptosis. Journal of immunology (Baltimore, Md. : 1950) 41 11342619
2009 PAR bZIP-bik is a novel transcriptional pathway that mediates oxidative stress-induced apoptosis in fibroblasts. Cell death and differentiation 37 19219069
2005 Caspase-independent induction of apoptosis in human melanoma cells by the proapoptotic Bcl-2-related protein Nbk / Bik. Oncogene 34 16007125
2001 The pro-apoptotic protein, Bik, exhibits potent antitumor activity that is dependent on its BH3 domain. Molecular cancer therapeutics 33 12467227
2019 HDAC4 Levels Control Sensibility toward Cisplatin in Gastric Cancer via the p53-p73/BIK Pathway. Cancers 32 31703394
2006 Transcriptional activation of the proapoptotic bik gene by E2F proteins in cancer cells. FEBS letters 32 17027756
2017 Plumbagin sensitizes breast cancer cells to tamoxifen-induced cell death through GRP78 inhibition and Bik upregulation. Scientific reports 30 28287102
2016 Osteopontin-stimulated apoptosis in cardiac myocytes involves oxidative stress and mitochondrial death pathway: role of a pro-apoptotic protein BIK. Molecular and cellular biochemistry 28 27262843
2023 TMEM215 Prevents Endothelial Cell Apoptosis in Vessel Regression by Blunting BIK-Regulated ER-to-Mitochondrial Ca Influx. Circulation research 27 37750320
2010 BH3-only protein Bik is involved in both apoptosis induction and sensitivity to oxidative stress in multiple myeloma. British journal of cancer 26 21063407
2000 GnRH-Bik/Bax/Bak chimeric proteins target and kill adenocarcinoma cells; the general use of pro-apoptotic proteins of the Bcl-2 family as novel killing components of targeting chimeric proteins. Apoptosis : an international journal on programmed cell death 26 11303912
2019 Upregulation of miR-1306-5p decreases cerebral ischemia/reperfusion injury in vitro by targeting BIK. Bioscience, biotechnology, and biochemistry 25 31460837
2017 Bik reduces hyperplastic cells by increasing Bak and activating DAPk1 to juxtapose ER and mitochondria. Nature communications 25 28986568
2014 Reversal of Mutant KRAS-Mediated Apoptosis Resistance by Concurrent Noxa/Bik Induction and Bcl-2/Bcl-xL Antagonism in Colon Cancer Cells. Molecular cancer research : MCR 24 25548100
2000 Structural analysis of the human pro-apoptotic gene Bik: chromosomal localization, genomic organization and localization of promoter sequences. Gene 23 10974546
2019 BIK ubiquitination by the E3 ligase Cul5-ASB11 determines cell fate during cellular stress. The Journal of cell biology 21 31387940
2017 Biphasic ROS production, p53 and BIK dictate the mode of cell death in response to DNA damage in colon cancer cells. PloS one 20 28796811
2014 Repression of the proapoptotic cellular BIK/NBK gene by Epstein-Barr virus antagonizes transforming growth factor β1-induced B-cell apoptosis. Journal of virology 19 24554662
2005 Suppression of pancreatic tumor progression by systemic delivery of a pancreatic-cancer-specific promoter driven Bik mutant. Cancer letters 19 15953675
2015 Induction of BCL2-Interacting Killer, BIK, is Mediated for Anti-Cancer Activity of Curcumin in Human Head and Neck Squamous Cell Carcinoma Cells. Journal of Cancer 17 25767602
2012 The proteasome inhibitor MG132 potentiates TRAIL receptor agonist-induced apoptosis by stabilizing tBid and Bik in human head and neck squamous cell carcinoma cells. Experimental cell research 17 22513214
2018 MicroRNA 486-3p directly targets BIK and regulates apoptosis and invasion in colorectal cancer cells. OncoTargets and therapy 15 30584337
2017 Autophagy regulatory molecule, TMEM74, interacts with BIK and inhibits BIK-induced apoptosis. Cellular signalling 15 28412412
2013 BH3-only proteins Noxa, Bik, Bmf, and Bid activate Bax and Bak indirectly when studied in yeast model. FEMS yeast research 15 23991648
2017 BIK is involved in BRAF/MEK inhibitor induced apoptosis in melanoma cell lines. Cancer letters 14 28720543
2017 Activation of Casein Kinase II by Gallic Acid Induces BIK-BAX/BAK-Mediated ER Ca++-ROS-Dependent Apoptosis of Human Oral Cancer Cells. Frontiers in physiology 14 29033852
2013 Suppression of the death gene BIK is a critical factor for resistance to tamoxifen in MCF-7 breast cancer cells. International journal of oncology 14 24100375
2017 Blocking Bcl-2 resolves IL-13-mediated mucous cell hyperplasia in a Bik-dependent manner. The Journal of allergy and clinical immunology 13 28784260
2006 5-Aza-2'-deoxycytidine and depsipeptide synergistically induce expression of BIK (BCL2-interacting killer). Biochemical and biophysical research communications 13 17064661
2021 Long non-coding RNA TUG1 knockdown prevents neurons from death to alleviate acute spinal cord injury via the microRNA-338/BIK axis. Bioengineered 12 34517787
2016 Bik Mediates Caspase-Dependent Cleavage of Viral Proteins to Promote Influenza A Virus Infection. American journal of respiratory cell and molecular biology 11 26437021
2008 The endoplasmic reticulum (ER)-target protein Bik induces Hep3B cells apoptosis by the depletion of the ER Ca2+ stores. Molecular and cellular biochemistry 11 18299962
2006 Mutant Bik expression mediated by the enhanced minimal topoisomerase IIalpha promoter selectively suppressed breast tumors in an animal model. Cancer gene therapy 11 16514421
2015 Bik subcellular localization in response to oxidative stress induced by chemotherapy, in Two different breast cancer cell lines and a Non-tumorigenic epithelial cell line. Journal of applied toxicology : JAT 10 26059411
2012 Neither loss of Bik alone, nor combined loss of Bik and Noxa, accelerate murine lymphoma development or render lymphoma cells resistant to DNA damaging drugs. Cell death & disease 10 22573037
2023 Bik promotes proteasomal degradation to control low-grade inflammation. The Journal of clinical investigation 9 38113109
2018 Biodistribution and Internal Radiation Dosimetry of 99mTc-IDA-D-[c(RGDfK)]2 (BIK-505), a Novel SPECT Radiotracer for the Imaging of Integrin αvβ3 Expression. Cancer biotherapy & radiopharmaceuticals 9 30133309
2007 Apoptosis induced by BIK was decreased with RNA interference of caspase-12. Biochemical and biophysical research communications 9 17574210
2007 Mutant Bik gene transferred by cationic liposome inhibits peritoneal disseminated murine colon cancer. Clinical & experimental metastasis 9 17636408
2023 Endoplasmic reticulum protein BIK binds to and inhibits mitochondria-localized antiapoptotic proteins. The Journal of biological chemistry 8 36603764
2014 Combination of lenalidomide with vitamin D3 induces apoptosis in mantle cell lymphoma via demethylation of BIK. Cell death & disease 8 25165875
2015 Breast cancer cell line MDA-MB-231 miRNA profile expression after BIK interference: BIK involvement in autophagy. Tumour biology : the journal of the International Society for Oncodevelopmental Biology and Medicine 7 26662110
2014 NS5B induces up-regulation of the BH3-only protein, BIK, essential for the hepatitis C virus RNA replication and viral release. Virology 7 25463603
2012 BIK (NBK) is a mediator of the sensitivity of Fanconi anaemia group C lymphoblastoid cell lines to interstrand DNA cross-linking agents. The Biochemical journal 7 22873408
2014 BikDDA, a mutant of Bik with longer half-life expression protein, can be a novel therapeutic gene for triple-negative breast cancer. PloS one 6 24637719
2009 BAK, BAX, and NBK/BIK proapoptotic gene alterations in Iranian patients with ataxia telangiectasia. Journal of clinical immunology 6 19898928
2024 MyoD1 promotes the transcription of BIK and plays an apoptosis-promoting role in the development of gastric cancer. Cell cycle (Georgetown, Tex.) 5 38701194
2023 Independent role of caspases and Bik in augmenting influenza A virus replication in airway epithelial cells and mice. Virology journal 5 37095508
2022 Copy number amplification-activated long non-coding RNA LINC00662 epigenetically inhibits BIK by interacting with EZH2 to regulate tumorigenesis in non-small cell lung cancer. Journal of Cancer 5 35371316
2015 Involvement of multiple cellular pathways in regulating resistance to tamoxifen in BIK-suppressed MCF-7 cells. Tumour biology : the journal of the International Society for Oncodevelopmental Biology and Medicine 5 25861752
2016 Low BIK outside-inside-out interactive inflammation immune-induced transcription-dependent apoptosis through FUT3-PMM2-SQSTM1-SFN-ZNF384. Immunologic research 4 26423071
2014 The increase in BIK expression following ERK1/2 pathway inhibition is a consequence of G₁ cell-cycle arrest and not a direct effect on BIK protein stability. The Biochemical journal 4 24527759
2025 BIK polymorphism and proteasome regulation unveil host risk factor for severe influenza. Proceedings of the National Academy of Sciences of the United States of America 3 40627391
2021 Casein kinase II activates Bik to induce death of hyperplastic mucous cells in a cell cycle-dependent manner. Journal of cellular physiology 3 34741311
2018 Does the BCL-2 family member BIK control lung carcinogenesis? Molecular & cellular oncology 3 30250907
2021 Expression of bik cluster and production of bikaverin by Fusarium oxysporum f. sp. lycopersici grown using two alternate nitrogen sources. International microbiology : the official journal of the Spanish Society for Microbiology 2 34455510
2021 Rhomboid domain containing 1 promotes the growth of non-small cell lung cancer through the activation of EGFR and regulation of the BIK-mediated apoptosis. Neoplasma 2 34962825
2025 Confirmation of BIK and SAMHD1 as Prostate Cancer Susceptibility Genes. The Prostate 1 40825105
2025 Polymorphism of BIK as a Host Risk Factor for Severe Influenza. DNA and cell biology 1 40971288
2024 Reduced Bik expression drives low-grade airway inflammation and increased risk for COPD in females. The Journal of clinical investigation 1 38357926

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