Affinage

SERPINB9

Serpin B9 · UniProt P50453

Length
376 aa
Mass
42.4 kDa
Annotated
2026-04-28
65 papers in source corpus 22 papers cited in narrative 22 extracted findings

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

SERPINB9 (PI-9) is an intracellular ovalbumin-family serpin that serves as the principal endogenous inhibitor of granzyme B, thereby protecting cytotoxic lymphocytes, bystander cells, and immune-privileged tissues from granzyme B–mediated apoptosis, while its expression in tumors enables immune evasion. SERPINB9 forms inhibitory complexes with granzyme B via its reactive center loop (P1 Glu residue), blocking granzyme B nuclear import and cytotoxic function, and additionally inhibits caspase-1, caspase-8, and caspase-10 through separable substrate specificities — a disease-associated A329S variant retains granzyme B inhibition but loses caspase-1 inhibition (PMID:11485349, PMID:17479112, PMID:26992230, PMID:15791691). The protein shuttles between cytoplasm and nucleus via a nonconventional import pathway and Crm1-dependent nuclear export, and is reversibly inactivated by reactive oxygen species through vicinal disulfide bond formation in its reactive center loop (PMID:11463822, PMID:26670609). Beyond granzyme B neutralization, SERPINB9 has a granzyme B–independent role in dendritic cell antigen cross-presentation by maintaining CIITA expression and MHC class II levels, and its genetic ablation in tumors or hosts restores T cell–mediated antitumor immunity (PMID:22801574, PMID:41160211, PMID:33242418, PMID:37258521).

Mechanistic history

Synthesis pass · year-by-year structured walk · 19 steps
  1. 1998 Medium

    Determining the genomic organization of SERPINB9 established it as a member of the ovalbumin-family serpin cluster on chromosome 6p25, providing the structural framework for subsequent functional studies.

    Evidence BAC/YAC mapping and exon-intron sequencing of the 6p25 locus

    PMID:9858835

    Open questions at the time
    • Regulatory elements and promoter characterization not defined
    • Evolutionary conservation of the cluster not assessed
  2. 2001 High

    Demonstration that SERPINB9 shuttles between cytoplasm and nucleus via nonconventional import and Crm1-dependent export revealed that this serpin accesses both compartments, raising the question of whether it protects against granzyme B in distinct subcellular locations.

    Evidence GFP-fusion imaging, subcellular fractionation, in vitro nuclear transport assays, and leptomycin B treatment in cytotoxic lymphocytes, endothelial cells, and epithelial cells

    PMID:11463822

    Open questions at the time
    • Nuclear function of SERPINB9 not established
    • Import receptor identity unknown
  3. 2001 Medium

    Identification of SERPINB9 as a granzyme B inhibitor in endothelial and mesothelial cells, inducible by inflammatory stimuli, established the bystander-protection model.

    Evidence Immunohistochemistry, recombinant granzyme B binding assay, PMA stimulation of mRNA and protein

    PMID:11485349

    Open questions at the time
    • In vivo bystander protection not yet demonstrated
    • Mechanism of PMA-mediated transcriptional induction not resolved
  4. 2005 Medium

    Showing that SERPINB9–granzyme B complexation blocks importin-β recognition and alters granzyme B nuclear entry established a second protective mechanism beyond direct protease inhibition — preventing nuclear accumulation of the killer protease.

    Evidence Quantitative yeast two-hybrid and in vitro nuclear import reconstitution with recombinant importins

    PMID:15791691

    Open questions at the time
    • Physiological relevance of import blockade versus direct inhibition not quantified in living cells
    • Whether SERPINB9–GrB complexes are degraded after formation is unknown
  5. 2007 High

    Extending SERPINB9's substrate repertoire to caspase-8 and caspase-10 via its P1 Glu residue showed it protects against extrinsic apoptosis pathways (TNF, TRAIL, FasL), not just granzyme B, broadening its anti-apoptotic role.

    Evidence Death-receptor ligand assays, P1 Glu→Ala mutagenesis, direct interaction assays with caspase-8 and caspase-10

    PMID:17479112

    Open questions at the time
    • Relative physiological importance of caspase versus granzyme B inhibition unclear
    • Kinetic parameters for caspase inhibition not fully defined
  6. 2007 High

    Genetic epistasis in vivo (perforin-KO, GrB-KO, NK-depleted mice) demonstrated that granzyme B activity from NK cells triggers hepatocyte Serpinb9 induction and that Serpinb9 loss accelerates granzyme B–dependent liver injury, establishing the protective axis in a solid organ.

    Evidence In vivo siRNA knockdown, multiple knockout mouse strains, adenoviral infection liver injury model

    PMID:17685438 PMID:17982045

    Open questions at the time
    • Transcription factor mediating GrB-triggered induction not identified
    • Whether this protective circuit operates in other solid organs not tested
  7. 2011 High

    Reciprocal loss- and gain-of-function experiments in mesenchymal stem cells confirmed that SERPINB9 cell-autonomously protects non-immune cells from NK cell–mediated granzyme B killing, extending the bystander model to stem cell biology.

    Evidence siRNA knockdown and retroviral overexpression of PI-9 in MSCs, NK cell cytotoxicity assay

    PMID:21795594

    Open questions at the time
    • Whether SERPINB9 levels in MSCs are dynamically regulated in vivo is unknown
  8. 2011 Medium

    Identification of innate viral dsRNA sensors (TLR3, MDA5, RIG-I) and NF-κB as inducers of SERPINB9 in renal epithelial cells linked pathogen sensing to pre-emptive granzyme B defense.

    Evidence Stimulation with specific dsRNA ligands, NF-κB inhibitor in primary human tubular epithelial cells, kidney transplant biopsies

    PMID:22167597

    Open questions at the time
    • NF-κB binding site in the SERPINB9 promoter not mapped
    • Relative contribution of each sensor in vivo not determined
  9. 2012 High

    Serpinb9-deficient DCs failed at MHC-I cross-presentation even in GrB-deficient backgrounds, revealing a granzyme B–independent function and opening a new mechanistic dimension for this serpin in adaptive immunity.

    Evidence Sb9-KO and Sb9/GrB double-KO mice, in vivo and ex vivo cross-presentation assays

    PMID:22801574

    Open questions at the time
    • Molecular target of SERPINB9 in the cross-presentation pathway unknown at this point
    • Whether this involves a protease substrate or scaffolding function unclear
  10. 2014 High

    Establishing that lysosomal membrane permeabilization releases granzyme B into the cytosol of activated lymphocytes, where endogenous Serpinb9 neutralizes it, defined the cell-intrinsic self-protection mechanism in killer cells during restimulation.

    Evidence Sb9-KO mice, pharmacological lysosomal stressors, live-cell imaging, GrB-KO controls, Ectromelia virus infection

    PMID:24488096

    Open questions at the time
    • Stoichiometric threshold of Sb9 versus GrB for protection not quantified
    • Fate of Sb9–GrB complexes in cytosol not tracked
  11. 2015 High

    Discovery that ROS reversibly inactivate SERPINB9 via a vicinal disulfide bond in the reactive center loop established a redox-sensing regulatory switch, explaining how oxidative stress in inflammation or tumors could disable granzyme B defense.

    Evidence Site-directed mutagenesis of RCL cysteines, in vitro ROS exposure, domain-swap into SERPINA1 scaffold

    PMID:26670609

    Open questions at the time
    • In vivo relevance of ROS-mediated inactivation not demonstrated
    • Whether reducing systems regenerate active SERPINB9 in cells not shown
  12. 2016 High

    A natural A329S variant that retains granzyme B inhibition but loses caspase-1 inhibition demonstrated separable substrate specificities and linked caspase-1 inhibition to autoinflammatory disease prevention, expanding SERPINB9's role to inflammasome regulation.

    Evidence Patient-derived cells with A329S variant, caspase-1 and GrB inhibition assays, IL-1β release measurement in monocytes

    PMID:26992230

    Open questions at the time
    • Full spectrum of Mendelian disease caused by SERPINB9 variants not established
    • Structural basis for differential substrate recognition at position 329 unknown
  13. 2016 Medium

    Reporter-mouse experiments showed that Serpinb9 expression marks the cross-presentation–competent DC subset, reinforcing its functional role and identifying it as a biomarker for this specialized DC population.

    Evidence GFP knockin reporter mouse under Sb9 promoter, flow sorting and cross-presentation assay

    PMID:28024184

    Open questions at the time
    • Causal mechanism by which Serpinb9 supports cross-presentation still unclear
    • Whether expression level is merely correlative or instructive not fully resolved
  14. 2017 High

    In vivo viral challenge confirmed that Serpinb9-null NK cells and CD8+ T cells undergo excessive granzyme B–dependent apoptosis, demonstrating that the Serpinb9–GrB axis governs cytotoxic lymphocyte homeostasis during infection.

    Evidence Serpinb9-KO/GFP reporter mice infected with Ectromelia virus, flow cytometry and apoptosis analysis

    PMID:28722018

    Open questions at the time
    • Whether chronic infections show cumulative lymphocyte attrition due to Sb9 deficiency not tested
  15. 2020 High

    Dual genetic ablation of Serpinb9 in tumor cells and host demonstrated that SERPINB9 enables immune evasion on both sides — tumor-intrinsic protection from GrB-mediated death and host-side support of immunosuppressive cells — establishing SERPINB9 as a therapeutic target.

    Evidence Sb9-KO mice and Sb9-KO tumor cells, tumor growth assays, TME immune phenotyping

    PMID:33242418

    Open questions at the time
    • Pharmacological inhibitors of SERPINB9 not yet developed
    • Whether Sb9 loss in host causes autoimmune toxicity not assessed
  16. 2023 High

    Unbiased in vivo CRISPR screens independently validated SERPINB9 as an immune evasion gene in lung cancer, confirming the genetic findings with an orthogonal discovery approach.

    Evidence In vivo CRISPR/Cas9 pooled screen in mouse lung cancer, functional validation

    PMID:37258521

    Open questions at the time
    • Context-dependency across tumor types not fully explored
  17. 2024 Medium

    Identification of the CA9/tumor acidosis axis as an upstream inducer of SERPINB9 in hypoxic tumors, and ATF-3 as a mediator of gemcitabine-induced SERPINB9 upregulation, began to map the transcriptional regulatory network in cancer contexts.

    Evidence siRNA knockdown of CA9 and SERPINB9, hypoxia assays, ATF-3 transcription factor analysis, in vivo tumor models

    PMID:38413363 PMID:40325025

    Open questions at the time
    • Complete promoter/enhancer architecture of SERPINB9 in tumors not defined
    • Interaction between NF-κB and ATF-3 pathways in SERPINB9 regulation not addressed
  18. 2024 Medium

    Engineering a SERPINB9 variant with broadened caspase specificity and overexpressing it in CAR T cells improved persistence and antitumor efficacy, providing therapeutic proof-of-concept for the cytoprotective function.

    Evidence Engineered SB9(CAS) variant in primary T cells, allorejection and cytotoxicity assays in vitro and in vivo

    PMID:38833270

    Open questions at the time
    • Long-term safety of engineered SERPINB9 variants in clinical settings unknown
    • Whether broadened specificity variant loses selectivity for unwanted proteases not tested
  19. 2025 Medium

    Identification of CIITA as a downstream target of SERPINB9 in macrophages — where SERPINB9 maintains CIITA expression and MHC-II surface display required for Th1 differentiation — provided a molecular mechanism for its granzyme B–independent immune role.

    Evidence SerpinB9-KO BMDMs, CIITA knockdown and overexpression rescue, MHC-II flow cytometry, Th1 differentiation assays

    PMID:41160211

    Open questions at the time
    • How SERPINB9 maintains CIITA expression mechanistically (transcriptional stabilization vs. protease target) is unknown
    • Whether the same CIITA axis operates in DCs for cross-presentation not tested

Open questions

Synthesis pass · forward-looking unresolved questions
  • The molecular mechanism by which SERPINB9 supports antigen cross-presentation and CIITA maintenance — whether through inhibition of an as-yet-unidentified protease, a scaffolding function, or another activity — remains the central open question.
  • No protease substrate identified for the GrB-independent function
  • No structural model of SERPINB9 with any substrate beyond granzyme B
  • No selective small-molecule inhibitor of SERPINB9 exists for therapeutic or tool-compound use

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0098772 molecular function regulator activity 9
Localization
GO:0005829 cytosol 2 GO:0005634 nucleus 1
Pathway
R-HSA-168256 Immune System 6 R-HSA-5357801 Programmed Cell Death 5
Partners
CASP1CASP10CASP8CIITAGZMBXPO1

Evidence

Reading pass · 22 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2001 PI-9 (SERPINB9) is present in both the cytoplasm and nucleus of cytotoxic lymphocytes, endothelial cells, and epithelial cells. Nuclear import requires cytosolic factors but not ATP, does not involve binding to an intranuclear component, and occurs via a nonconventional (non-classical NLS) pathway. Nuclear export requires the export factor Crm1 (leptomycin B-sensitive), demonstrating active nucleocytoplasmic shuttling. Subcellular fractionation, fluorescence microscopy of GFP-fusion chimeric proteins (~70 kDa, too large for passive diffusion), in vitro nuclear transport assays, leptomycin B treatment Molecular and cellular biology High 11463822
2001 SERPINB9 (PI-9) is an intracellular serpin expressed in endothelial and mesothelial cells where it binds and inhibits granzyme B, proposed to protect bystander cells from misdirected granzyme B during immune responses. PI-9 expression is upregulated by PMA (inflammatory stimulus) at mRNA and protein level. Immunohistochemistry, binding assay with recombinant granzyme B, mRNA analysis Cellular immunology Medium 11485349
2005 PI-9 (SERPINB9) complexation with granzyme B prevents granzyme B recognition by importin-beta but not importin-alpha, and eliminates the apparent requirement of importin-alpha for granzyme B nuclear import, thereby modulating granzyme B's nuclear entry and associated apoptosis. Quantitative yeast two-hybrid assay, direct binding assays, in vitro nuclear import reconstitution with recombinant importins and antibody inhibition Journal of cellular biochemistry Medium 15791691
2007 PI-9 (SERPINB9) inhibits TNF-, TRAIL-, and FasL-mediated apoptosis by directly interacting with intermediate active forms of caspase-8 and caspase-10. Inhibition requires the reactive center P1 residue (Glu); a Glu→Ala mutation abolishes inhibition, consistent with classical serpin-protease interaction. Cell death assays with death-receptor ligands, site-directed mutagenesis of reactive center loop, direct interaction assays with caspase-8 and caspase-10 Cell death and differentiation High 17479112
2007 Serpinb9 (SPI-6, mouse ortholog of SERPINB9) expression in hepatocytes is selectively upregulated by IFN-alpha and during adenoviral infection in a manner dependent on NK cell infiltration, perforin expression, and enzymatically active granzyme B — identifying granzyme B activity from NK cells as the trigger for hepatocyte serpinb9 induction. In vivo siRNA knockdown, mouse genetic knockouts (perforin-deficient, granzyme B-deficient, NK-depleted), qRT-PCR in liver tissue Journal of immunology High 17982045
2007 Serpinb9/SPI-6 (mouse ortholog) protects hepatocytes from granzyme B-dependent NK cell-mediated killing in vivo. siRNA-mediated knockdown of SPI-6 accelerated granzyme B-dependent liver injury and acute liver failure following adenoviral infection, effects absent in granzyme B-deficient or NK-depleted mice. In vivo siRNA administration, genetic knockout mice (granzyme B-deficient), NK cell depletion, ALT measurement, adenoviral infection model Hepatology High 17685438
2011 SERPINB9 (PI-9) expression in human mesenchymal stem cells (MSCs) is a major defense mechanism against granzyme B-mediated NK cell destruction. siRNA knockdown of PI-9 increased MSC death; retroviral overexpression of PI-9 protected MSCs from NK cell killing. siRNA knockdown, retroviral transgenic overexpression, NK cell cytotoxicity assay Journal of immunology High 21795594
2011 SerpinB9 expression in renal tubular epithelial cells is induced by triggering of viral dsRNA sensors TLR3, MDA5, and RIG-I via NF-κB activation, independent of Type I interferon, leading to increased threshold for granzyme B-mediated apoptosis. Stimulation of primary human TECs with poly(I:C) and specific dsRNA receptor ligands, NF-κB inhibitor, mRNA and protein analysis, kidney transplant biopsy analysis Nephrology, dialysis, transplantation Medium 22167597
2012 Serpinb9 (Sb9/Spi6, mouse ortholog) is required for dendritic cell (DC)-mediated antigen cross-presentation via MHC class I. Sb9-deficient mice fail to generate cytotoxic T-cell responses to cell-associated antigens but maintain normal MHC-II presentation. This role is granzyme B-independent, as it is present in mice deficient in both Sb9 and granzyme B. Gene-targeted knockout mice (Sb9-KO, Sb9/GrB double KO), in vivo and ex vivo antigen cross-presentation assays, MHC-I and MHC-II T-cell response measurement Immunology and cell biology High 22801574
2014 Serpinb9 (Sb9) protects cytotoxic lymphocytes against granzyme B-mediated apoptosis triggered by lysosomal membrane permeabilization (LMP). Restimulation of activated lymphocytes induces LMP, releasing granzyme B from lysosome-related organelles into the cytosol; endogenous Sb9 neutralizes this GrB to promote cell survival. Effectiveness of Sb9 protection diminishes as LMP extent increases. Gene-targeted Sb9-knockout mice, pharmacological lysosomal stressors (sphingosine, Leu-Leu-methyl-ester), live-cell imaging, GrB-deficient mice, Ectromelia virus infection model Cell death and differentiation High 24488096
2015 SerpinB9 is reversibly inactivated by reactive oxygen species (ROS) through formation of a vicinal disulfide bond between a conserved cysteine pair (P1-P1' in rodents; P1'-P2' in other mammals) in the reactive center loop. This ROS-mediated oxidation prevents GrB inhibition. Converting the cysteine pair to serines produces a functional, ROS-resistant GrB inhibitor, demonstrating this is the key regulatory mechanism. Site-directed mutagenesis of reactive center loop cysteines, in vitro ROS exposure assays, biochemical inhibition assays, transfer of Sb9 reactive center loop residues into SERPINA1 scaffold The Journal of biological chemistry High 26670609
2016 SerpinB9 inhibits caspase-1, thereby restraining IL-1β maturation and release in human monocytes. A disease-associated variant (A329S) retains granzyme B inhibitory activity but loses caspase-1 inhibitory activity, demonstrating separable substrate specificities and linking caspase-1 inhibition to autoinflammatory disease prevention. Patient-derived cells with serpinB9 A329S variant, serpinB9 overexpression in monocytic cells, caspase-1 and granzyme B inhibition assays, IL-1β release measurement Oncotarget High 26992230
2016 Serpinb9 expression marks the cross-presentation-competent subset of dendritic cells. Among CD8+ DCs, only the Sb9-high subset is capable of antigen cross-presentation, establishing Sb9 as both a functional marker and participant in DC cross-presentation biology. GFP knockin reporter mouse under Sb9 promoter, flow cytometric sorting of DC subsets by Sb9-GFP level, functional cross-presentation assays Molecular immunology Medium 28024184
2017 Serpinb9 is vital for survival of NK cells and CD8+ T cells during poxvirus (Ectromelia) infection. Serpinb9-null NK cells exhibit higher granzyme B-mediated apoptosis during infection, resulting in fewer mature NK cells with reduced cytotoxic potential, demonstrating that the Serpinb9-GrB axis regulates cytotoxic lymphocyte homeostasis in vivo. Serpinb9 knockout mouse (GFP knockin reporter), Ectromelia virus infection, flow cytometric analysis of NK and T cell populations, apoptosis assays Immunology and cell biology High 28722018
2020 Genetic ablation of SerpinB9 in tumor cells causes granzyme B-dependent tumor cell death, and Sb9-deficient hosts show T cell-based protective immunity associated with reduced GrB-expressing immunosuppressive cells in the tumor microenvironment. Maximum protection occurs when both tumor and host lack Sb9. Genetic knockout (Sb9-KO mice and Sb9-KO tumor cells), granzyme B-dependent death assays, tumor growth monitoring, immune phenotyping of TME Cell High 33242418
2023 In vivo CRISPR/Cas9 screens in mouse lung cancer identified Serpinb9 as a validated immune evasion factor; Serpinb9 loss sensitizes tumor cells to T cell-mediated killing in vivo. In vivo CRISPR/Cas9 pooled screen in mouse lung cancer models, validation with loss- and gain-of-function experiments, T cell cytotoxicity assays Nature communications High 37258521
2022 Genetic ablation of SERPINB9 in human NSCLC tumor cells reverts resistance to T cell killing, while overexpression reduces T cell sensitivity, confirming that SERPINB9 intrinsically confers resistance to cytotoxic T lymphocyte-mediated killing via granzyme B inhibition. Genetic ablation and overexpression in matched MHC I/antigen:TCR panel, T cell cytotoxicity assays Oncoimmunology Medium 36465485
2024 Overexpression of an engineered SERPINB9 variant with broadened caspase specificity (SB9(CAS)) in allogeneic CAR T cells significantly reduced rejection by NK/T cells and increased resistance to activation-induced cell death, improving T cell persistence and antitumor activity without causing autonomous growth. Engineered SERPINB9 variant overexpression in primary T cells, allorejection and cytotoxicity assays in vitro and in vivo, inducible suicide switch validation Cancer immunology research Medium 38833270
2024 Hypoxia-associated carbonic anhydrase 9 (CA9) upregulates serpinB9 in cancer cells via tumor acidosis, enhancing resistance to cytotoxic T cells. siRNA knockdown of serpinB9 restored T cell sensitivity, and CA9 gene knockdown inhibited hypoxia-induced serpinB9 expression, placing serpinB9 downstream of the CA9/acidosis axis. siRNA knockdown of serpinB9 and CA9, hypoxia induction, CA9 gene overexpression, T cell cytotoxicity assays, gene microarray, in vivo tumor growth assays Cancer science Medium 38413363
2025 Gemcitabine treatment upregulates SERPINB9 through the transcription factor ATF-3, and gemcitabine also induces granzyme B expression. Knockout or knockdown of SERPINB9 enhances tumor cell response to gemcitabine, identifying the GzmB/SERPINB9 axis as a regulator of chemosensitivity. SERPINB9 knockout/knockdown, gemcitabine treatment, ATF-3 transcription factor analysis, tumor cell viability assays, in vivo pancreatic cancer models with siRNA nanocarrier co-delivery Nature communications Medium 40325025
2025 In β-glucan (WGP)-induced macrophages, SerpinB9 maintains CIITA expression, which is required for surface MHC-II expression and the capacity to induce Th1 cell differentiation. SerpinB9 knockout reduces CIITA and MHC-II; CIITA overexpression rescues MHC-II expression and Th1-inducing ability in SerpinB9-KO macrophages. SerpinB9 knockout BMDMs, WGP stimulation, transcriptome analysis, CIITA knockdown and overexpression, flow cytometry for MHC-II, TNF-α measurement, Th1 differentiation assay Immunologic research Medium 41160211
1998 The human SERPINB9 gene (PI9) maps to a ~200-kb region on chromosome 6p25 and has seven exons and six introns, a structure almost identical to PI6 in the same cluster. Gene order is established as: telomere-PI6-PI9-ELANH2-centromere. Fine mapping of BAC/YAC clones, exon-intron structure determination by sequencing Cytogenetics and cell genetics Medium 9858835

Source papers

Stage 0 corpus · 65 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
1999 CAP3: A DNA sequence assembly program. Genome research 3482 10508846
2005 The broad-spectrum blast resistance gene Pi9 encodes a nucleotide-binding site-leucine-rich repeat protein and is a member of a multigene family in rice. Genetics 293 16387888
2015 Comparative genomics identifies the Magnaporthe oryzae avirulence effector AvrPi9 that triggers Pi9-mediated blast resistance in rice. The New phytologist 126 25659573
2001 Nucleocytoplasmic distribution of the ovalbumin serpin PI-9 requires a nonconventional nuclear import pathway and the export factor Crm1. Molecular and cellular biology 98 11463822
2002 Two broad-spectrum blast resistance genes, Pi9( t) and Pi2( t), are physically linked on rice chromosome 6. Molecular genetics and genomics : MGG 95 12111554
2020 Direct Tumor Killing and Immunotherapy through Anti-SerpinB9 Therapy. Cell 74 33242418
2006 Genetic characterization and fine mapping of the blast resistance locus Pigm(t) tightly linked to Pi2 and Pi9 in a broad-spectrum resistant Chinese variety. TAG. Theoretical and applied genetics. Theoretische und angewandte Genetik 72 16832648
2001 The granzyme B inhibitor, PI-9, is present in endothelial and mesothelial cells, suggesting that it protects bystander cells during immune responses. Cellular immunology 69 11485349
2006 Expression of the granzyme B inhibitor PI9 predicts outcome in nasal NK/T-cell lymphoma: results of a Western series of 48 patients treated with first-line polychemotherapy within the Groupe d'Etude des Lymphomes de l'Adulte (GELA) trials. Blood 53 17077322
2006 Chicken genomics resource: sequencing and annotation of 35,407 ESTs from single and multiple tissue cDNA libraries and CAP3 assembly of a chicken gene index. Physiological genomics 49 16554550
2012 The identification of Pi50(t), a new member of the rice blast resistance Pi2/Pi9 multigene family. TAG. Theoretical and applied genetics. Theoretische und angewandte Genetik 45 22270148
2004 Hyperexpression of the granzyme B inhibitor PI-9 in human renal allografts: a potential mechanism for stable renal function in patients with subclinical rejection. Kidney international 43 15458434
2012 Increased proteinase inhibitor-9 (PI-9) and reduced granzyme B in lung cancer: mechanism for immune evasion? Lung cancer (Amsterdam, Netherlands) 41 22387007
2005 Lymphomas are sensitive to perforin-dependent cytotoxic pathways despite expression of PI-9 and overexpression of bcl-2. Blood 39 16373664
2017 Understanding Host-Pathogen Interactions with Expression Profiling of NILs Carrying Rice-Blast Resistance Pi9 Gene. Frontiers in plant science 36 28280498
2016 The analysis of estrogen receptor-α positive breast cancer stem-like cells unveils a high expression of the serpin proteinase inhibitor PI-9: Possible regulatory mechanisms. International journal of oncology 35 27121069
2014 The granzyme B-Serpinb9 axis controls the fate of lymphocytes after lysosomal stress. Cell death and differentiation 35 24488096
2023 In vivo CRISPR screens reveal Serpinb9 and Adam2 as regulators of immune therapy response in lung cancer. Nature communications 34 37258521
2023 The ANIP1-OsWRKY62 module regulates both basal defense and Pi9-mediated immunity against Magnaporthe oryzae in rice. Molecular plant 33 36872602
2011 Inhibition of Granzyme B by PI-9 protects prostate cancer cells from apoptosis. The Prostate 30 21919028
2022 Inhibition of SerpinB9 to enhance granzyme B-based tumor therapy by using a modified biomimetic nanoplatform with a cascade strategy. Biomaterials 29 35963816
2005 The granzyme B inhibitor proteinase inhibitor 9 (PI9) is expressed by human mast cells. European journal of immunology 29 15739160
2016 Allele-specific marker-based assessment revealed that the rice blast resistance genes Pi2 and Pi9 have not been widely deployed in Chinese indica rice cultivars. Rice (New York, N.Y.) 27 27142801
2005 The granzyme B inhibitor SERPINB9 (protease inhibitor 9) circulates in blood and increases on primary cytomegalovirus infection after renal transplantation. The Journal of infectious diseases 27 16267761
2007 Ectopic expression of the serine protease inhibitor PI9 modulates death receptor-mediated apoptosis. Cell death and differentiation 26 17479112
2011 The novel role of SERPINB9 in cytotoxic protection of human mesenchymal stem cells. Journal of immunology (Baltimore, Md. : 1950) 25 21795594
2016 Serpinb9 is a marker of antigen cross-presenting dendritic cells. Molecular immunology 23 28024184
2022 SERPINB9 is commonly amplified and high expression in cancer cells correlates with poor immune checkpoint blockade response. Oncoimmunology 22 36465485
2007 The role of serpinb9/serine protease inhibitor 6 in preventing granzyme B-dependent hepatotoxicity. Hepatology (Baltimore, Md.) 22 17685438
2011 SerpinB9 expression in human renal tubular epithelial cells is induced by triggering of the viral dsRNA sensors TLR3, MDA5 and RIG-I. Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association 21 22167597
2006 Modulation of the granzyme B inhibitor proteinase inhibitor 9 (PI-9) by activation of lymphocytes and monocytes in vitro and by Epstein-Barr virus and bacterial infection. Clinical and experimental immunology 21 16487253
2004 The granzyme B inhibitor PI-9 is differentially expressed in all main subtypes of pediatric acute lymphoblastic leukemias. Haematologica 21 15531453
2017 A pro-survival role for the intracellular granzyme B inhibitor Serpinb9 in natural killer cells during poxvirus infection. Immunology and cell biology 20 28722018
2012 Serpinb9 (Spi6)-deficient mice are impaired in dendritic cell-mediated antigen cross-presentation. Immunology and cell biology 20 22801574
2022 Decreased GZMB, NRP1, ITPR1, and SERPINB9 Transcripts Lead to Reduced Regulatory T Cells Suppressive Capacity in Generalized Vitiligo Patients. Journal of immunology research 19 36157881
2016 Reduced serpinB9-mediated caspase-1 inhibition can contribute to autoinflammatory disease. Oncotarget 17 26992230
2015 A Novel Serpin Regulatory Mechanism: SerpinB9 IS REVERSIBLY INHIBITED BY VICINAL DISULFIDE BOND FORMATION IN THE REACTIVE CENTER LOOP. The Journal of biological chemistry 17 26670609
1998 A serpin gene cluster on human chromosome 6p25 contains PI6, PI9 and ELANH2 which have a common structure almost identical to the 18q21 ovalbumin serpin genes. Cytogenetics and cell genetics 17 9858835
2010 Expression of proteinase inhibitor-9/serpinB9 in non-small cell lung carcinoma cells and tissues. International journal of oncology 16 19956856
2022 Protocatechuic Acid-Based Supramolecular Hydrogel Targets SerpinB9 to Achieve Local Chemotherapy for OSCC. ACS applied materials & interfaces 15 35904511
2007 Intrahepatic lymphocyte expression of dipeptidyl peptidase I-processed granzyme B and perforin induces hepatocyte expression of serine proteinase inhibitor 6 (Serpinb9/SPI-6). Journal of immunology (Baltimore, Md. : 1950) 15 17982045
2005 The granzyme B inhibitor, PI-9, is differentially expressed during placental development and up-regulated in hydatidiform moles. Placenta 15 16310039
2021 Proteomics-Based Approach Reveals the Involvement of SERPINB9 in Recurrent and Relapsed Multiple Myeloma. Journal of proteome research 13 33650432
2024 The biological function of Serpinb9 and Serpinb9-based therapy. Frontiers in immunology 12 38966643
2020 Identification of Novel Alleles of the Rice Blast-Resistance Gene Pi9 through Sequence-Based Allele Mining. Rice (New York, N.Y.) 11 33284383
2019 Disrupted regulation of serpinB9 in circulating T cells is associated with an increased risk for post-transplant skin cancer. Clinical and experimental immunology 10 31059128
2015 Genome-wide haplotype association analysis identifies SERPINB9, SERPINE2, GAK, and HSP90B1 as novel risk genes for oral squamous cell carcinoma. Tumour biology : the journal of the International Society for Oncodevelopmental Biology and Medicine 10 26318431
2005 Interaction of the nuclear localizing cytolytic granule serine protease granzyme B with importin alpha or beta: modulation by the serpin inhibitor PI-9. Journal of cellular biochemistry 10 15791691
2016 Allele Mining and Selective Patterns of Pi9 Gene in a Set of Rice Landraces from India. Frontiers in plant science 8 28018384
2025 Rational development of gemcitabine-based nanoplatform for targeting SERPINB9/Granzyme B axis to overcome chemo-immune-resistance. Nature communications 7 40325025
2016 Identification of a Pi9-Containing Rice Germplasm with a Newly Developed Robust Marker. Phytopathology 6 27050577
2006 Influence of pentoxifylline on natural cytotoxicity and expression of granzymes and PI-9, a specific granzyme B inhibitor. International journal of molecular medicine 6 16328022
2025 Microbiota-reprogrammed phosphatidylcholine inactivates cytotoxic CD8 T cells through UFMylation via exosomal SerpinB9 in multiple myeloma. Nature communications 5 40128181
2024 Single-cell landscape identified SERPINB9 as a key player contributing to stemness and metastasis in non-seminomas. Cell death & disease 5 39528470
2023 Emergence of Rice Blast AVR-Pi9 Resistance Breaking Haplotypes in Yunnan Province, China. Life (Basel, Switzerland) 5 37374103
2021 HER2-PI9 and HER2-I12: two novel and functionally active splice variants of the oncogene HER2 in breast cancer. Journal of cancer research and clinical oncology 5 34136934
2024 Hypoxia-related carbonic anhydrase 9 induces serpinB9 expression in cancer cells and apoptosis in T cells via acidosis. Cancer science 4 38413363
2023 Kidney-Specific Membrane-Bound Serine Proteases CAP1/Prss8 and CAP3/St14 Affect ENaC Subunit Abundances but Not Its Activity. Cells 4 37830556
2025 Biomimetic self-assembly nanoparticles inhibit serpinB9 and synergistically enhance COD-induced ferroptosis for cancer therapy. Materials today. Bio 2 40605985
2024 Overexpression of an Engineered SERPINB9 Enhances Allogeneic T-cell Persistence and Efficacy. Cancer immunology research 2 38833270
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