Affinage

BCL2L10

Bcl-2-like protein 10 · UniProt Q9HD36

Length
204 aa
Mass
23.2 kDa
Annotated
2026-04-28
100 papers in source corpus 28 papers cited in narrative 28 extracted findings

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

BCL2L10 is an anti-apoptotic Bcl-2 family member that guards against mitochondrial apoptosis, autophagy, and mitophagy through distinct molecular interactions. It selectively binds and neutralizes pro-apoptotic Bax (but not Bak) via a restricted BH3-binding groove, with specificity determined by the Bax BH3 domain and key groove residues (L86, R96), and additionally inhibits IP3R-mediated ER Ca²⁺ release through its BH4 domain at ER and mitochondria-associated membranes, thereby suppressing Ca²⁺-driven apoptotic signaling (PMID:11689480, PMID:11278245, PMID:12921534, PMID:29330143, PMID:27995898). BCL2L10 also negatively regulates Beclin 1-dependent autophagy and Parkin-mediated mitophagy through direct binding of these effectors (PMID:22498477, PMID:30635551). Its protein stability is controlled by K48-linked polyubiquitination at K128 targeting it for proteasomal degradation, counteracted by stabilizing interactions with Ubiquilin1 and UBQLN4, while the orphan nuclear receptor Nur77 converts BCL2L10 from anti-apoptotic to pro-apoptotic upon binding (PMID:23563182, PMID:22233804, PMID:34245648, PMID:17227826). Transcription of BCL2L10 is driven by STAT3, and its expression confers chemotherapy resistance in melanoma and myeloid malignancies (PMID:33396645, PMID:22577154).

Mechanistic history

Synthesis pass · year-by-year structured walk · 15 steps
  1. 1998 High

    The initial identification of Diva/BCL2L10 as a Bcl-2 family member that binds Apaf-1 and promotes apoptosis established that this gene encoded an unexpected direct modulator of the apoptosome scaffold, distinct from typical pro- or anti-apoptotic members.

    Evidence Co-IP and overexpression apoptosis assays with BH3 deletion mutants in 293T and other cell lines

    PMID:9829980

    Open questions at the time
    • Pro-apoptotic function via Apaf-1 binding was later contradicted by anti-apoptotic data in human systems
    • Binding specificity for Apaf-1 versus Bcl-2 family members not reconciled across species
  2. 1999 High

    Demonstration that mouse Boo/BCL2L10 forms multimeric complexes with Apaf-1 and caspase-9 that are disrupted by BH3-only proteins Bak and Bik resolved its role as an anti-apoptotic guardian of the apoptosome complex.

    Evidence Co-IP, yeast two-hybrid, Apaf-1 domain mapping, and overexpression apoptosis assays

    PMID:9878060

    Open questions at the time
    • Physiological stoichiometry of the Boo–Apaf-1–caspase-9 complex not determined
    • Whether Apaf-1 interaction is the primary anti-apoptotic mechanism in vivo remained unclear
  3. 2001 High

    Three independent studies established that human BCL2L10 is an anti-apoptotic protein that selectively binds Bax but not Bak, blocks the mitochondrial (but not death receptor) apoptosis pathway, and requires both BH4 and transmembrane domains for function, defining its mechanism as distinct from Bcl-2/Bcl-XL.

    Evidence Domain deletion mutagenesis, Co-IP, GST pulldown, flow cytometry for apoptosis and ΔΨm, GFP live-cell imaging in multiple cell lines

    PMID:11278245 PMID:11566354 PMID:11689480

    Open questions at the time
    • Structural basis for Bax selectivity over Bak not yet determined
    • Translocation from non-mitochondrial sites to mitochondria observed but trigger mechanism unknown
  4. 2002 High

    Genetic knockout of Diva in mice revealed functional redundancy with other Bcl-2 family members, demonstrating that BCL2L10 is dispensable for normal ovarian development and genotoxic apoptosis in vivo.

    Evidence Gene targeting (knockout mouse), histological analysis, apoptosis assays after genotoxic stress

    PMID:12215543

    Open questions at the time
    • Compensatory mechanisms not identified
    • Tissue-specific or stress-specific non-redundant roles not tested beyond ovary and genotoxic stress
  5. 2003 High

    Structure–function analysis of the BH3-binding groove revealed that BCL2L10's selectivity for Bax over Bak is determined by the BH3 domain of Bax itself, and specific groove residues (L86, R96) are required for both Bax binding and anti-apoptotic function.

    Evidence BH3 chimeric mutants, alanine-scanning and structure-based mutagenesis, Co-IP, cell death assays

    PMID:12921534

    Open questions at the time
    • No crystal or NMR structure of BCL-B alone or with Bax at this time
    • Whether this selectivity operates in endogenous protein contexts not shown
  6. 2007 High

    Discovery that orphan nuclear receptor Nur77/TR3 binds BCL2L10 with highest affinity among anti-apoptotic Bcl-2 proteins and converts it to a pro-apoptotic effector revealed a novel regulatory switch that could override BCL2L10 survival function.

    Evidence Reciprocal endogenous Co-IP in myeloma cells, siRNA epistasis, fluorescence polarization binding assays

    PMID:17227826

    Open questions at the time
    • Structural mechanism of phenotypic conversion not determined
    • Whether Nur77 exposes Bax or disrupts Apaf-1 complexes unknown
  7. 2009 High

    BCL2L10 was found to be the predominant Bcl-2 family transcript in oocytes, and its knockdown causes metaphase I arrest with impaired MPF activity, establishing a non-apoptotic role in oocyte meiotic maturation.

    Evidence dsRNA microinjection in mouse oocytes, immunofluorescence, MPF/MAPK activity assays, antibody neutralization

    PMID:19439730 PMID:19551325

    Open questions at the time
    • How BCL2L10 regulates MPF activity is mechanistically undefined
    • Whether this function is Bax-dependent or independent not addressed
  8. 2010 High

    BCL2L10 was shown to bind the BH3 domain of Beclin 1 and suppress autophagy, with knockdown triggering Beclin 1/LC3/ATG5-dependent autophagic cell death, establishing BCL2L10 as a dual inhibitor of apoptosis and autophagy.

    Evidence Reciprocal Co-IP, autophagy flux assays, siRNA knockdown with genetic epistasis using ATG5 and BECN1

    PMID:22498477

    Open questions at the time
    • Relative contributions of anti-apoptotic versus anti-autophagic functions in physiological contexts not dissected
    • Whether autophagy inhibition requires the same BH3 groove as Bax binding unknown
  9. 2012 High

    Crystal structure of BCL-B bound to Bim BH3 peptide at 1.9 Å revealed an unstructured loop between helices α5–α6 unique to BCL2L10, and biophysical profiling showed high-affinity binding restricted to Bim and Bik among BH3-only proteins, distinguishing it from all other anti-apoptotic family members.

    Evidence X-ray crystallography (1.9 Å), fluorescence polarization with BH3 peptide panel, cell-based apoptosis assays

    PMID:23235460

    Open questions at the time
    • Structure of BCL-B bound to full-length Bax not available
    • Functional significance of the α5–α6 loop not fully resolved
  10. 2012 High

    Identification of K48-linked polyubiquitination at K128 as the primary signal for BCL2L10 proteasomal degradation, and stabilization by Ubiquilin1-mediated monoubiquitination, established the post-translational control circuit governing BCL2L10 protein levels.

    Evidence Mass spectrometry, linkage-specific ubiquitin antibodies, lysineless mutant with enhanced anti-apoptotic activity, cycloheximide chase, immunoaffinity purification

    PMID:22233804 PMID:23563182

    Open questions at the time
    • E3 ligase responsible for K48-linked ubiquitination at K128 not identified
    • Whether mono- and polyubiquitination compete at the same lysines not resolved
  11. 2016 High

    The IRBIT–BCL2L10 interaction at mitochondria-associated membranes (MAMs) revealed a phosphorylation-dependent regulatory switch: under normal conditions both cooperatively inhibit IP3R Ca²⁺ release, but upon apoptotic stress, dephosphorylated IRBIT antagonizes BCL2L10 and promotes ER-to-mitochondria Ca²⁺ transfer to execute apoptosis.

    Evidence Co-IP, MAM fractionation, Ca²⁺ imaging, phosphorylation analysis, apoptosis assays

    PMID:27995898

    Open questions at the time
    • Identity of the phosphatase that dephosphorylates IRBIT under stress not known
    • Whether this MAM mechanism operates in all cell types not tested
  12. 2018 High

    Demonstration that BCL2L10 inhibits IP3R-mediated Ca²⁺ release specifically through its BH4 domain interacting with the ligand-binding domain of IP3R1/3 at the ER, with BH4-mimetic peptides disrupting this interaction and suppressing breast cancer growth in vivo, defined a druggable ER-localized anti-apoptotic mechanism.

    Evidence Co-IP, Ca²⁺ release assays, subcellular fractionation, BH4 domain mutagenesis, BH4 peptide competition, xenograft model

    PMID:29330143

    Open questions at the time
    • Structural details of BH4–IP3R interface not resolved at atomic level
    • Whether BH4 peptides affect other BH4-dependent interactions not assessed
  13. 2019 Medium

    BCL2L10 was shown to suppress Parkin-mediated mitophagy by directly binding phosphorylated Parkin and inhibiting its phosphorylation, expanding BCL2L10's protective repertoire to mitochondrial quality control in hepatic stellate cells.

    Evidence Co-IP of BCL-B with phospho-Parkin, knockdown and overexpression, mitophagy assays, in vivo mouse fibrosis model

    PMID:30635551

    Open questions at the time
    • Mechanism by which BCL2L10 inhibits Parkin phosphorylation (PINK1 competition?) not determined
    • Single lab finding in hepatic stellate cells; generalizability unclear
    • Reciprocal validation with endogenous proteins limited
  14. 2020 Medium

    Identification of STAT3 as a direct transcriptional activator of BCL2L10 through functional promoter elements linked BCL2L10 upregulation to oncogenic signaling and chemotherapy resistance in melanoma.

    Evidence Promoter reporter assays, site-directed mutagenesis of STAT3 elements, ChIP, siRNA knockdown, drug resistance assays

    PMID:33396645

    Open questions at the time
    • Whether STAT3 drives BCL2L10 in non-melanoma contexts not established
    • Additional transcription factors regulating BCL2L10 not characterized
  15. 2021 Medium

    UBQLN4 was identified as a second Ubiquilin family stabilizer of BCL2L10 and linked to ATM-dependent DNA damage signaling, connecting BCL2L10 protein stability to the DNA damage response in mesothelioma.

    Evidence Genetic screening, Co-IP, ATM substrate identification, cell death assays upon DNA damage

    PMID:34245648

    Open questions at the time
    • Whether UBQLN1 and UBQLN4 act redundantly or in different contexts not resolved
    • How ATM phosphorylation of UBQLN4 modulates BCL2L10 binding not mechanistically defined

Open questions

Synthesis pass · forward-looking unresolved questions
  • The E3 ubiquitin ligase targeting BCL2L10 for K48-linked degradation remains unidentified, the structural basis of Nur77-mediated phenotypic conversion is unknown, and how BCL2L10 regulates MPF activity during oocyte meiosis has no mechanistic explanation.
  • E3 ligase for K48-linked ubiquitination at K128 not identified
  • No structure of BCL2L10 with full-length Bax or Nur77
  • Mechanism linking BCL2L10 to MPF regulation in oocytes completely unknown

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0098772 molecular function regulator activity 8
Localization
GO:0005739 mitochondrion 4 GO:0005783 endoplasmic reticulum 2 GO:0005829 cytosol 1
Pathway
R-HSA-5357801 Programmed Cell Death 10 R-HSA-9612973 Autophagy 2 R-HSA-1852241 Organelle biogenesis and maintenance 1
Partners
APAF1BAXBECN1ITPR1NR4A1PRKNUBQLN1UBQLN4

Evidence

Reading pass · 28 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
1998 Diva (BCL2L10 mouse ortholog) promotes apoptosis independently of its BH3 domain by directly binding Apaf-1, thereby preventing Bcl-XL from interacting with Apaf-1/caspase-9. Diva did not bind cellular Bcl-2, Bcl-XL, Bcl-w, Mcl-1, or A1/Bfl-1, but was inhibited by viral Bcl-2 (vBcl-2) encoded by KSHV. Co-immunoprecipitation, overexpression apoptosis assays, BH3 deletion mutagenesis, 293T/Ramsey/T47D cell death assays The Journal of Biological Chemistry High 9829980
1999 Mouse Boo (BCL2L10 ortholog) is an anti-apoptotic protein that homodimerizes and heterodimerizes with pro- and anti-apoptotic Bcl-2 family members, interacts with Apaf-1, and forms a multimeric complex with Apaf-1 and caspase-9. Pro-apoptotic Bak and Bik disrupt the Boo–Apaf-1 association. Boo binds three distinct regions of Apaf-1. Co-immunoprecipitation, yeast two-hybrid, overexpression apoptosis assays The EMBO Journal High 9878060
2001 Human BCL2L10 (Bcl2-L-10) blocks the mitochondrial apoptosis pathway (cytochrome c release, caspase-3 activation, mitochondrial membrane potential collapse) induced by IL-3 withdrawal and Bax overexpression, but cannot block TNFα-induced (death receptor) apoptosis. Both the BH4 domain and the transmembrane domain are required for anti-apoptotic function. Transient transfection, flow cytometry for apoptosis and ΔΨm, caspase-3 activation assay, domain deletion mutants Human Molecular Genetics High 11689480
2001 Bcl-B (human BCL2L10) selectively binds Bax but not Bak, suppresses Bax-induced but not Bak-induced apoptosis, and requires its C-terminal transmembrane domain for association with intracellular organelles and full anti-apoptotic function. It also binds Bcl-2 and Bcl-XL. Co-immunoprecipitation, GST pulldown, transient transfection apoptosis assays, TM-deletion mutants The Journal of Biological Chemistry High 11278245
2001 Human Boo/Diva (BCL2L10) promotes cell death in HeLa and 293 cells; GFP-tagged Boo/Diva translocates from a non-mitochondrial localization to mitochondria during vincristine-induced apoptosis. Bcl-XL interacts with Boo but cannot protect cells from Boo/Diva-induced death. GFP live-cell imaging, co-immunoprecipitation, transient transfection cell death assays Biochimica et Biophysica Acta Medium 11566354
2002 Genetic inactivation of Diva (BCL2L10) in mice shows that Diva is dispensable for normal ovarian development, fertility, and genotoxic stress-induced apoptosis, indicating functional redundancy with other Bcl-2 family members in vivo. Gene targeting (knockout mouse), histological analysis, apoptosis assays after genotoxic stress Molecular and Cellular Biology High 12215543
2003 The differential binding specificity of Bcl-B (BCL2L10) for Bax (but not Bak) is determined by the BH3 domain of Bax: Bcl-B binds chimeric Bak containing Bax's BH3 domain, and Bcl-B BH3-pocket mutants (L86A, R96Q) lose Bax-binding and fail to suppress Bax-induced apoptosis, demonstrating tight structure–function correlation. BH3 chimeric mutants, alanine-scanning mutagenesis, structure-based BH3-pocket mutagenesis, co-immunoprecipitation, cell death assays The Biochemical Journal High 12921534
2007 Orphan nuclear receptor Nur77/TR3 binds BCL-B (BCL2L10) with the highest affinity among anti-apoptotic Bcl-2 family members and converts its phenotype from anti-apoptotic to pro-apoptotic. Endogenous BCL-B and Nur77 associate in RPMI 8226 myeloma cells, and BCL-B knockdown abolishes Nur77-induced apoptosis. Co-immunoprecipitation, siRNA knockdown, overexpression cell death assays, fluorescence polarization binding assays Blood High 17227826
2007 NM23-H2 interacts with Diva (BCL2L10 mouse ortholog) in a transmembrane domain-dependent manner and down-regulates Diva protein levels; NM23-H2 knockdown restores Diva expression and increases Diva-mediated apoptotic activity. Yeast two-hybrid, co-immunoprecipitation, siRNA knockdown, overexpression apoptosis assays Biochemical and Biophysical Research Communications Medium 17532299
2008 BCL-B (BCL2L10) shows strong preference for binding and suppressing Bax over Bak, as assessed by co-immunoprecipitation, GST pulldown, and fluorescence polarization with BH3 peptides. Mcl-1 shows the reciprocal preference for Bak, distinguishing these two anti-apoptotic proteins from Bcl-2, Bcl-XL, Bcl-w, and Bfl-1. Co-immunoprecipitation, GST pulldown, fluorescence polarization with synthetic BH3 peptides, overexpression apoptosis assays The Journal of Biological Chemistry High 18178565
2009 BCL2L10 is the predominant maternally loaded Bcl-2 family transcript in oocytes and early embryos, associates with TCTP and mitochondria with stage-specific redistribution along the pericortical ooplasm, co-localizes with BAX in dying oocytes, and its neutralization accelerates oocyte death. mRNA expression profiling, immunofluorescence, co-localization imaging, antibody neutralization, fractionation Journal of Molecular Medicine Medium 19551325
2009 BCL2L10 knockdown by siRNA in mouse germinal vesicle oocytes causes metaphase I arrest with spindle and chromosome abnormalities, impairs maturation-promoting factor (MPF) activity, but does not affect MAPK activity, indicating a specific role for BCL2L10 in the MI-to-MII oocyte transition. Microinjection of dsRNA, real-time PCR, Western blot, immunofluorescence, MPF/MAPK activity assays Biology of Reproduction High 19439730
2009 HIP1R directly interacts with BCL2L10 (human Diva/BCL-B) in a manner requiring the ANTH and THATCH domains of HIP1R; HIP1R overexpression induces BAK-dependent (but BAX-independent) mitochondrial apoptosis and augments BCL2L10–caspase-9 interaction. Yeast two-hybrid, co-immunoprecipitation, Far-Western analysis, domain deletion mutants, mitochondrial membrane potential assay, caspase-9 activation Cellular Physiology and Biochemistry Medium 19255499
2010 BCL2L10 interacts with the BH3 domain of BECN1 (Beclin 1) and suppresses autophagy induced by multiple stimuli; BCL2L10 knockdown triggers BECN1/LC3/ATG5-dependent autophagic cell death, establishing BCL2L10 as a negative regulator of autophagy. Co-immunoprecipitation, overexpression and siRNA knockdown, autophagy flux assays (LC3), flow cytometry, ATG5/BECN1 knockdown epistasis Autophagy High 22498477
2010 BCL2L10 overexpression in gastric cancer cells induces apoptosis via the mitochondrial pathway and suppresses tumor growth; BCL2L10 siRNA activates PI3K-Akt signaling to promote proliferation, indicating context-dependent dual roles in gastric cancer cells. Flow cytometry, fluorescence staining, murine xenograft, Western blot, PI3K pathway inhibitors, siRNA The Journal of Pathology Medium 21171085
2010 Diva (BCL2L10 mouse ortholog) interacts with Harakiri (HRK, a BH3-only protein) via a surface equivalent to the canonical BH3-binding groove of anti-apoptotic Bcl-2 proteins, as mapped by NMR spectroscopy and molecular docking. ELISA, NMR spectroscopy, molecular docking, circular dichroism PLoS One High 21209886
2011 BCL2L10 contains two divergent indel regions: an N-terminal extension and a loop between predicted α5-α6 helices. The α5-α6 interhelical region in human BCL2L10 has acquired negatively charged residues consistent with a calcium-binding motif; deletion of the N-terminal extension had no functional impact, while mutations in the α5-α6 loop affected protein behavior. Phylogenetic analysis, truncation and site-directed mutagenesis, biochemical assays, cell biological functional assays Molecular Biology and Evolution Medium 21705382
2012 BCL2L10 (BCLb) is stabilized by Ubiquilin1 (UBQLN1) at the post-translational level; Ubqln1 promotes monoubiquitination of BCLb on multiple lysine residues and relocalizes it to the cytosol. In the absence of Ubqln1 interaction, BCLb protein is rapidly degraded after protein synthesis inhibition. Immunoaffinity purification, mass spectrometry, cycloheximide chase, co-immunoprecipitation, protein stability assays Proceedings of the National Academy of Sciences USA High 22233804
2012 BCL-B (BCL2L10) is polyubiquitinated via K48-linked chains at lysine K128 (and potentially K119/K120) within the loop between BH1 and BH2 domains, targeting it for proteasomal degradation. A lysineless BCL-B mutant has fivefold higher protein expression and enhanced anti-apoptotic activity. Mutagenesis, mass spectrometry, linkage-specific polyubiquitin antibodies, proteasome inhibitor assays, Western blot Oncogene High 23563182
2012 BCL-B (BCL2L10) has high-affinity interactions restricted to BH3-only proteins Bim and Bik only (not Bad, Bik alone broadly, PUMA, NOXA, tBid, HRK); crystal structure of BCL-B:Bim complex at 1.9 Å resolution revealed an unstructured loop insertion between helices α5 and α6 distinguishing BCL-B from other Bcl-2 family members. Crystal structure (1.9 Å), fluorescence polarization binding assays, cell-based apoptosis assays Cell Death & Disease High 23235460
2012 BCL-B (BCL2L10) is not targeted by BH3-mimetic ABT-737 (which targets Bcl-2, Bcl-xL, Bcl-w); BCL-B-mediated apoptosis resistance is specifically overcome by BH3-only protein Noxa but not by Bim, PUMA, or truncated Bid, as demonstrated in human T-leukemic cells with inducible expression. Inducible expression, apoptosis assays, ABT-737 drug treatment, BH3-only protein knockin/knockdown Cell Death & Disease Medium 22875003
2013 BCL2L10 knockdown sensitizes AZA-resistant myeloid cells (SKM1-R) to azacitidine-induced cell death, linking elevated BCL2L10 expression to drug resistance in myeloid cells. siRNA knockdown, cell viability assays, flow cytometry Oncotarget Medium 22577154
2016 IRBIT interacts with BCL2L10 and they additively inhibit IP3R in physiological conditions. Upon apoptotic stress, IRBIT is dephosphorylated and becomes an inhibitor of BCL2L10. IRBIT and BCL2L10 associate in mitochondria-associated membranes (MAMs), and IRBIT promotes ER–mitochondria contact, facilitating massive Ca2+ transfer and apoptosis. Co-immunoprecipitation, IP3R binding assays, mitochondria-associated membrane fractionation, Ca2+ imaging, apoptosis assays, phosphorylation analysis eLife High 27995898
2018 BCL2L10 (Nrh) localizes to the endoplasmic reticulum and inhibits IP3R-mediated ER-Ca2+ release through BH4 domain-dependent interaction with the ligand-binding domain of IP3R type 1/3; disruption of Nrh/IP3R complexes by BH4 mimetic peptides inhibits breast cancer cell growth in vitro and in vivo. Co-immunoprecipitation, Ca2+ release assays, subcellular fractionation, domain mutagenesis, BH4 peptide competition, xenograft mouse model Cancer Research High 29330143
2019 BCL-B (BCL2L10) suppresses mitophagy in hepatic stellate cells by directly binding phosphorylated Parkin (a key mitophagy regulator) and inhibiting its phosphorylation; BCL-B knockdown increases both mitophagy and apoptosis in HSCs during hepatic fibrosis regression. Co-immunoprecipitation, Western blot for phospho-Parkin, BCL-B knockdown and overexpression, mitophagy assays, in vivo mouse fibrosis model Experimental & Molecular Medicine Medium 30635551
2019 BCL2L10 inhibits autophagy in hepatoma cells by binding Beclin 1 (BECN1), which reduces the interaction between Beclin 1 and PI3KC3, thereby downregulating PI3K/AKT-dependent autophagy. Co-immunoprecipitation, ELISA, immunofluorescence co-localization, autophagic flux assay (LC3B-II/P62), pathway inhibition Aging Medium 30696802
2020 BCL2L10 expression in melanoma is driven by STAT3-mediated transcription; functional STAT3-responsive elements in the BCL2L10 promoter were identified by reporter assays, site-directed mutagenesis, and ChIP analysis. BCL2L10 confers resistance to cisplatin and ABT-737, and its inhibition sensitizes melanoma cells to these agents. Reporter assays, site-directed mutagenesis, ChIP, siRNA knockdown, drug resistance assays, BRAF inhibitor combination Cancers Medium 33396645
2021 UBQLN4 interacts with and stabilizes BCL2L10 (and BCL2A1) in mesothelioma cells; UBQLN4 is identified as an ATM kinase substrate, and the UBQLN4–BCL2L10 interaction prevents mesothelioma cell apoptosis in response to DNA damage. Genetic screening, co-immunoprecipitation, ATM substrate identification, cell death assays upon DNA damage Molecular Oncology Medium 34245648

Source papers

Stage 0 corpus · 100 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2003 Development of a DIVA (Differentiating Infected from Vaccinated Animals) strategy using a vaccine containing a heterologous neuraminidase for the control of avian influenza. Avian pathology : journal of the W.V.P.A 157 12745380
1999 Diva vaccines that reduce virus transmission. Journal of biotechnology 153 10486928
1998 Diva, a Bcl-2 homologue that binds directly to Apaf-1 and induces BH3-independent cell death. The Journal of biological chemistry 144 9829980
1999 Boo, a novel negative regulator of cell death, interacts with Apaf-1. The EMBO journal 143 9878060
2008 Differential regulation of Bax and Bak by anti-apoptotic Bcl-2 family proteins Bcl-B and Mcl-1. The Journal of biological chemistry 113 18178565
2001 Bcl-B, a novel Bcl-2 family member that differentially binds and regulates Bax and Bak. The Journal of biological chemistry 104 11278245
2004 Generation of reassortant influenza vaccines by reverse genetics that allows utilization of a DIVA (Differentiating Infected from Vaccinated Animals) strategy for the control of avian influenza. Vaccine 89 15297071
2005 Overview of avian influenza DIVA test strategies. Biologicals : journal of the International Association of Biological Standardization 78 16257543
2012 Bcl-2 is a better ABT-737 target than Bcl-xL or Bcl-w and only Noxa overcomes resistance mediated by Mcl-1, Bfl-1, or Bcl-B. Cell death & disease 74 22875003
2018 Dancing with the Diva: Hsp90-Client Interactions. Journal of molecular biology 73 29782836
2012 BCL2L10 is a predictive factor for resistance to azacitidine in MDS and AML patients. Oncotarget 71 22577154
2007 Nur77 converts phenotype of Bcl-B, an antiapoptotic protein expressed in plasma cells and myeloma. Blood 71 17227826
2016 IRBIT controls apoptosis by interacting with the Bcl-2 homolog, Bcl2l10, and by promoting ER-mitochondria contact. eLife 62 27995898
2012 Ubiquitination, localization, and stability of an anti-apoptotic BCL2-like protein, BCL2L10/BCLb, are regulated by Ubiquilin1. Proceedings of the National Academy of Sciences of the United States of America 62 22233804
2012 The restricted binding repertoire of Bcl-B leaves Bim as the universal BH3-only prosurvival Bcl-2 protein antagonist. Cell death & disease 61 23235460
2001 Bcl2-L-10, a novel anti-apoptotic member of the Bcl-2 family, blocks apoptosis in the mitochondria death pathway but not in the death receptor pathway. Human molecular genetics 59 11689480
2021 Deletion of E184L, a Putative DIVA Target from the Pandemic Strain of African Swine Fever Virus, Produces a Reduction in Virulence and Protection against Virulent Challenge. Journal of virology 52 34668772
2019 The role of the apoptosis-related protein BCL-B in the regulation of mitophagy in hepatic stellate cells during the regression of liver fibrosis. Experimental & molecular medicine 51 30635551
2008 Bcl-B expression in human epithelial and nonepithelial malignancies. Clinical cancer research : an official journal of the American Association for Cancer Research 50 18483366
2012 The anti-apoptotic Bcl-B protein inhibits BECN1-dependent autophagic cell death. Autophagy 44 22498477
2014 Recombinant adenovirus expressing the haemagglutinin of Peste des petits ruminants virus (PPRV) protects goats against challenge with pathogenic virus; a DIVA vaccine for PPR. Veterinary research 42 24568545
2009 Oocytes and early embryos selectively express the survival factor BCL2L10. Journal of molecular medicine (Berlin, Germany) 37 19551325
2020 Aujeszky's Disease and the Development of the Marker/DIVA Vaccination Concept. Pathogens (Basel, Switzerland) 36 32664700
2018 Breast Cancer Targeting through Inhibition of the Endoplasmic Reticulum-Based Apoptosis Regulator Nrh/BCL2L10. Cancer research 36 29330143
2007 NM23-H2 involves in negative regulation of Diva and Bcl2L10 in apoptosis signaling. Biochemical and biophysical research communications 35 17532299
2006 Development of a DIVA subunit vaccine against Actinobacillus pleuropneumoniae infection. Vaccine 35 17027123
2008 Development of a porcine reproductive and respiratory syndrome virus differentiable (DIVA) strain through deletion of specific immunodominant epitopes. Vaccine 34 18538899
2010 BCL2L10 protein regulates apoptosis/proliferation through differential pathways in gastric cancer cells. The Journal of pathology 33 21171085
2001 Characterization of NR13-related human cell death regulator, Boo/Diva, in normal and cancer tissues. Biochimica et biophysica acta 32 11566354
2003 Characterization of the anti-apoptotic mechanism of Bcl-B. The Biochemical journal 31 12921534
2009 Role of Bcl2-like 10 (Bcl2l10) in Regulating Mouse Oocyte Maturation. Biology of reproduction 30 19439730
2022 Evaluation of the Deletion of MGF110-5L-6L on Swine Virulence from the Pandemic Strain of African Swine Fever Virus and Use as a DIVA Marker in Vaccine Candidate ASFV-G-ΔI177L. Journal of virology 29 35862688
2011 Raltegravir concentrations in the genital tract of HIV-1-infected women treated with a raltegravir-containing regimen (DIVA 01 study). Antimicrobial agents and chemotherapy 29 21444705
2006 Development and validation of an anti-N3 indirect immunofluorescent antibody test to be used as a companion diagnostic test in the framework of a "DIVA" vaccination strategy for avian influenza infections in poultry. Avian pathology : journal of the W.V.P.A 29 16595309
2015 Intermediate rough Brucella abortus S19Δper mutant is DIVA enable, safe to pregnant guinea pigs and confers protection to mice. Vaccine 28 25869887
2013 Virus-like particles: promising platforms with characteristics of DIVA for veterinary vaccine design. Comparative immunology, microbiology and infectious diseases 27 23561290
2010 Homology modeling and docking studies of human Bcl-2L10 protein. Journal of biomolecular structure & dynamics 27 20919753
2009 A DIVA system based on the detection of antibodies to non-structural protein 3 (NS3) of bluetongue virus. Veterinary microbiology 27 19233575
2008 DIVA diagnostic of Aujeszky's disease using an insect-derived virus glycoprotein E. Journal of virological methods 27 18638504
2002 Murine ovarian development is not affected by inactivation of the bcl-2 family member diva. Molecular and cellular biology 27 12215543
2022 Improving peripheral venous cannula insertion in children: a mixed methods study to develop the DIVA key. BMC health services research 26 35177041
2014 Strong protection induced by an experimental DIVA subunit vaccine against bluetongue virus serotype 8 in cattle. Vaccine 24 25312275
2021 The roles of MCP-1/CCR2 mediated macrophage recruitment and polarization in bladder outlet obstruction (BOO) induced bladder remodeling. International immunopharmacology 23 34311189
2016 Avian Influenza Virus and DIVA Strategies. Viral immunology 23 26900835
2016 BCL-B (BCL2L10) is overexpressed in patients suffering from multiple myeloma (MM) and drives an MM-like disease in transgenic mice. The Journal of experimental medicine 23 27455953
2014 VP2-serotyped live-attenuated bluetongue virus without NS3/NS3a expression provides serotype-specific protection and enables DIVA. Vaccine 23 25454873
2010 Differentiation of infected and vaccinated animals (DIVA) using the NS1 protein of avian influenza virus. Avian diseases 23 20521645
2021 Application of portable real-time recombinase-aided amplification (rt-RAA) assay in the clinical diagnosis of ASFV and prospective DIVA diagnosis. Applied microbiology and biotechnology 22 33835201
2012 Protective efficacy of crude virus-like particle vaccine against HPAI H5N1 in chickens and its application on DIVA strategy. Influenza and other respiratory viruses 22 22716302
2010 BCL2L10 is frequently silenced by promoter hypermethylation in gastric cancer. Oncology reports 22 20428828
2009 HIP1R interacts with a member of Bcl-2 family, BCL2L10, and induces BAK-dependent cell death. Cellular physiology and biochemistry : international journal of experimental cellular physiology, biochemistry, and pharmacology 22 19255499
2003 The DIVa maturase binding site in the yeast group II intron aI2 is essential for intron homing but not for in vivo splicing. Molecular and cellular biology 22 14612420
2022 Test performance data demonstrates utility of a cattle DIVA skin test reagent (DST-F) compatible with BCG vaccination. Scientific reports 21 35835806
2013 The BCL2L10 Leu21Arg variant and risk of therapy-related myeloid neoplasms and de novo myelodysplastic syndromes. Leukemia & lymphoma 21 24047476
2012 Performance of genotypic tropism testing on proviral DNA in clinical practice: results from the DIVA study group. The new microbiologica 21 22378549
2016 A DIVA vaccine for cross-protection against Salmonella. Vaccine 20 26836212
2021 Performance of the currently available DIVA real-time PCR assays in classical and recombinant lumpy skin disease viruses. Transboundary and emerging diseases 19 33253485
2020 BCL2L10 Is Overexpressed in Melanoma Downstream of STAT3 and Promotes Cisplatin and ABT-737 Resistance. Cancers 19 33396645
2016 Chimeric Bivalent Virus-Like Particle Vaccine for H5N1 HPAI and ND Confers Protection against a Lethal Challenge in Chickens and Allows a Strategy of Differentiating Infected from Vaccinated Animals (DIVA). PloS one 19 27626934
2012 RHCE*ceTI encodes partial c and partial e and is often in cis to RHD*DIVa. Transfusion 19 22804620
2011 Development of a combined canine distemper virus specific RT-PCR protocol for the differentiation of infected and vaccinated animals (DIVA) and genetic characterization of the hemagglutinin gene of seven Chinese strains demonstrated in dogs. Journal of virological methods 19 22108430
2016 BCL2L10 inhibits growth and metastasis of hepatocellular carcinoma both in vitro and in vivo. Molecular carcinogenesis 18 27770580
2011 Proteomic and immunoproteomic characterization of a DIVA subunit vaccine against Actinobacillus pleuropneumoniae. Proteome science 18 21507263
2018 MicroRNA-18a promotes hepatocellular carcinoma proliferation, migration, and invasion by targeting Bcl2L10. OncoTargets and therapy 17 30519035
2018 Boo-boos as the building blocks of pain expression: An observational examination of parental responses to everyday pain in toddlers. Canadian journal of pain = Revue canadienne de la douleur 17 35005368
2021 Safety and protective efficacy of Salmonella Pullorum spiC and rfaH deletion rough mutant as a live attenuated DIVA vaccine candidate. Poultry science 16 34991038
2019 BCL2L10/BECN1 modulates hepatoma cells autophagy by regulating PI3K/AKT signaling pathway. Aging 16 30696802
2019 Coastal flood risks in China through the 21st century - An application of DIVA. The Science of the total environment 16 31839315
2017 Salmonella DIVA vaccine reduces disease, colonization and shedding due to virulent S. Typhimurium infection in swine. Journal of medical microbiology 16 28516860
2015 Development of a competitive ELISA for NS3 antibodies as DIVA test accompanying the novel Disabled Infectious Single Animal (DISA) vaccine for Bluetongue. Vaccine 16 26387435
2013 Polyubiquitination and proteasomal turnover controls the anti-apoptotic activity of Bcl-B. Oncogene 16 23563182
2009 Comparative efficacy of North American and antigenically matched reverse genetics derived H5N9 DIVA marker vaccines against highly pathogenic Asian H5N1 avian influenza viruses in chickens. Vaccine 16 19686695
2001 Diva/Boo is a negative regulator of cell death in human glioma cells. FEBS letters 16 11557035
2010 Characterization of a novel interaction between Bcl-2 members Diva and Harakiri. PloS one 14 21209886
2023 Bcl-B: an "unknown" protein of the Bcl-2 family. Biology direct 13 37899453
2019 The potential of a DIVA-like recombinant vaccine composed by rNcSAG1 and rAtHsp81.2 against vertical transmission in a mouse model of congenital neosporosis. Acta tropica 13 31323195
2018 MicroRNA-101 protects bladder of BOO from hypoxia-induced fibrosis by attenuating TGF-β-smad2/3 signaling. IUBMB life 13 30549198
2010 Detection of Mycoplasma mycoides subsp. mycoides SC in bronchoalveolar lavage fluids of cows based on a TaqMan real-time PCR discriminating wild type strains from an lppQ(-) mutant vaccine strain used for DIVA-strategies. Journal of microbiological methods 13 20381545
2009 Generation and evaluation of an H9N1 influenza vaccine derived by reverse genetics that allows utilization of a DIVA strategy for control of H9N2 avian influenza. Archives of virology 13 19543688
2022 Prospective lipid-A altered live attenuated Salmonella Gallinarum confers protectivity, DIVA capability, safety and low endotoxicity against fowl typhoid. Veterinary microbiology 12 36113357
2013 Characterization of a serologic marker candidate for development of a live-attenuated DIVA vaccine against porcine reproductive and respiratory syndrome virus. Vaccine 12 23892102
2011 Development of DIVA (differentiation of infected from vaccinated animals) vaccines utilizing heterologous NA and NS1 protein strategies for the control of triple reassortant H3N2 influenza in turkeys. Vaccine 12 21907751
2021 Development of an Inactivated H7N9 Subtype Avian Influenza Serological DIVA Vaccine Using the Chimeric HA Epitope Approach. Microbiology spectrum 11 34585985
2021 Pentavalent Disabled Infectious Single Animal (DISA)/DIVA Vaccine Provides Protection in Sheep and Cattle against Different Serotypes of Bluetongue Virus. Vaccines 11 34696258
2020 A Novel Recombinant Newcastle Disease Virus Vectored DIVA Vaccine against Peste des Petits Ruminants in Goats. Vaccines 11 32354145
2014 DIVA vaccine properties of the live chimeric pestivirus strain CP7_E2gif. Veterinary microbiology 11 24629779
2012 Diva reduces cell death in response to oxidative stress and cytotoxicity. PloS one 11 22905226
2011 Characterization of unique signature sequences in the divergent maternal protein Bcl2l10. Molecular biology and evolution 11 21705382
2009 Novel use of a N2-specific enzyme-linked immunosorbent assay for differentiation of infected from vaccinated animals (DIVA)-based identification of avian influenza. Vaccine 11 19446190
2021 The Bluetongue Disabled Infectious Single Animal (DISA) Vaccine Platform Based on Deletion NS3/NS3a Protein Is Safe and Protective in Cattle and Enables DIVA. Viruses 10 34067226
2021 UBQLN4 is an ATM substrate that stabilizes the anti-apoptotic proteins BCL2A1 and BCL2L10 in mesothelioma. Molecular oncology 10 34245648
2013 Effect of a DIVA vaccine with and without in-feed use of coated calcium-butyrate on transmission of Salmonella Typhimurium in pigs. BMC veterinary research 10 24304918
2012 Etravirine concentrations in the cervicovaginal compartment in HIV-1-infected women receiving etravirine-containing antiretroviral therapy: DIVA 02 study. Antimicrobial agents and chemotherapy 10 22526321
2010 Population-based analysis of Actinobacillus pleuropneumoniae ApxIVA for use as a DIVA antigen. Vaccine 10 20483193
2008 A TR3/Nur77 peptide-based high-throughput fluorescence polarization screen for small molecule Bcl-B inhibitors. Journal of biomolecular screening 10 18626112
2022 Assessing an O-antigen deficient, live attenuated Salmonella Gallinarium strain that is DIVA compatible, environmentally safe, and protects chickens against fowl typhoid. Developmental and comparative immunology 9 35568244
2021 BOO induces fibrosis and EMT in urothelial cells which can be recapitulated in vitro through elevated storage and voiding pressure cycles. International urology and nephrology 9 34232473
2019 Differential viral accessibility (DIVA) identifies alterations in chromatin architecture through large-scale mapping of lentiviral integration sites. Nature protocols 9 30518911
2019 Bcl2l10 mediates the proliferation, invasion and migration of ovarian cancer cells. International journal of oncology 9 31894274
2018 The importance of area scaling with FACS DIVA software. Methods (San Diego, Calif.) 9 29371108