Affinage

GLB1

Beta-galactosidase · UniProt P16278

Round 2 corrected
Length
677 aa
Mass
76.1 kDa
Annotated
2026-04-28
130 papers in source corpus 11 papers cited in narrative 11 extracted findings

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

GLB1 encodes lysosomal β-D-galactosidase, an acid hydrolase that cleaves terminal β-galactosyl residues from glycosphingolipids, glycoproteins, and keratan sulfate, and whose deficiency causes the lysosomal storage disorder GM1 gangliosidosis through accumulation of GM1 ganglioside (PMID:5647842, PMID:31534909). Within the lysosome, GLB1 functions as part of a multienzyme complex with protective protein/cathepsin A (CTSA) and neuraminidase-1 (NEU1), and this association is required for neuraminidase catalytic activity (PMID:3922758, PMID:16314420). An alternatively spliced, enzymatically inactive 67-kDa isoform serves as the elastin/laminin-binding protein (EBP) on the cell surface, where it chaperones tropoelastin secretion and elastic fiber assembly by coordinating with CTSA and NEU1 to release tropoelastin upon exposure of galactosugars on microfibrils (PMID:8383699, PMID:9497360, PMID:16314420). The canonical lysosomal enzyme is also the molecular source of senescence-associated β-galactosidase (SA-β-gal) activity: GLB1 protein is upregulated during replicative and therapy-induced senescence, and its expression increases with chronological age in vivo (PMID:16626397, PMID:36396643).

Mechanistic history

Synthesis pass · year-by-year structured walk · 9 steps
  1. 1968 High

    Establishing the primary enzymatic defect: demonstrating that profound loss of β-galactosidase activity is the biochemical basis of generalized (GM1) gangliosidosis resolved the question of which enzyme is responsible for GM1 ganglioside catabolism.

    Evidence Enzymatic activity assay on patient tissue homogenates using synthetic and radiolabeled GM1 substrates

    PMID:5647842

    Open questions at the time
    • No molecular cloning or gene identification at this stage
    • Genotype–phenotype spectrum not yet explored
  2. 1985 High

    Identifying the lysosomal multienzyme complex: showing that β-galactosidase, protective protein/cathepsin A, and neuraminidase form a high-molecular-weight complex — and that the protective protein is essential for neuraminidase activity — explained the secondary neuraminidase deficiency in galactosialidosis and established GLB1 as a structural component of this complex.

    Evidence Affinity chromatography, immunotitration, and sucrose gradient centrifugation of human placental lysosomes

    PMID:3922758

    Open questions at the time
    • Stoichiometry and atomic structure of the complex unresolved
    • Mechanism by which protective protein activates neuraminidase not defined
  3. 1993 High

    Discovering the EBP splice variant: identifying an alternatively spliced, enzymatically inactive 67-kDa GLB1 product as the elastin/laminin-binding protein revealed a bifunctional gene with roles in both lysosomal catabolism and extracellular matrix biology.

    Evidence Antibody against the unique splice-variant peptide (S-GAL), Western blot, elastin/laminin affinity chromatography

    PMID:8383699

    Open questions at the time
    • Whether EBP functions independently or requires cofactors for elastic fiber assembly was unknown
    • In vivo relevance of EBP not yet tested
  4. 1998 High

    Functional reconstitution of EBP: expressing full-length S-gal cDNA in EBP-deficient smooth muscle cells restored cell-surface elastin binding, adhesion, and elastic fiber assembly, definitively proving the splice variant is the functional EBP.

    Evidence cDNA transfection into COS-1 and EBP-deficient vascular smooth muscle cells with functional rescue assays

    PMID:9497360

    Open questions at the time
    • Molecular mechanism triggering tropoelastin release from EBP not resolved
    • Role of associated proteins in elastic fiber assembly not defined
  5. 2005 High

    Elucidating the EBP-mediated elastic fiber assembly mechanism: showing that the EBP/CTSA/NEU1 cell-surface complex uses neuraminidase-1 to desialylate microfibrillar glycoproteins, exposing galactosugars that trigger tropoelastin release, provided a unified mechanism linking the lysosomal multienzyme complex components to extracellular elastogenesis.

    Evidence Co-immunoprecipitation, sialidase inhibitors, neuraminidase-1 reconstitution in patient fibroblasts, chick embryo elastogenesis assays

    PMID:16314420

    Open questions at the time
    • Structural basis of EBP galectin-domain recognition of galactosugars unresolved
    • Recycling dynamics of EBP at the cell surface not quantified
  6. 2006 High

    Identifying the molecular origin of SA-β-gal: demonstrating that senescence-associated β-galactosidase activity derives from GLB1 — via GLB1 shRNA knockdown and GM1-gangliosidosis patient cells — resolved the long-standing question of the enzyme's identity and showed that GLB1 protein is upregulated during senescence.

    Evidence shRNA knockdown of GLB1, SA-β-gal assay at pH 6.0, GM1-gangliosidosis patient fibroblasts, Western blot

    PMID:16626397

    Open questions at the time
    • Mechanism driving GLB1 transcriptional or translational upregulation in senescence not identified
    • Functional significance of elevated β-galactosidase in senescent cells (beyond biomarker) unknown
  7. 2010 Medium

    Mapping genotype–phenotype correlations: systematic analysis of 28 GLB1 mutations showed that residual enzyme activity and subcellular localization of mutant proteins predict clinical severity, advancing understanding of how specific mutations translate to disease spectrum in GM1 gangliosidosis.

    Evidence Overexpression of mutant alleles in COS-1 cells, immunofluorescence localization in patient fibroblasts, enzyme activity assays

    PMID:20175788

    Open questions at the time
    • No in vivo validation of genotype–phenotype predictions
    • Structural basis for misfolding of specific mutants not determined
  8. 2019 High

    Proving gene therapy feasibility in a human CNS model: CRISPR knockout of GLB1 in iPSC-derived cerebral organoids recapitulated GM1 ganglioside accumulation, and AAV9-GLB1 delivery rescued enzymatic activity and reduced storage, providing preclinical evidence for gene replacement therapy.

    Evidence CRISPR/Cas9 knockout in cerebral organoids, AAV9-GLB1 microinjection, enzyme and ganglioside quantification

    PMID:31534909

    Open questions at the time
    • Long-term durability of gene therapy correction not assessed
    • Cross-correction efficiency in complex brain tissue architecture not evaluated
  9. 2022 High

    Validating GLB1 as an in vivo senescence biomarker: an endogenous Glb1-2A-mCherry knock-in reporter demonstrated that GLB1 expression increases linearly with age and exponentially in pathological senescence, and that senolytic treatment reduces this signal, establishing GLB1 as a quantitative marker of senescent cell burden in living animals.

    Evidence CRISPR knock-in reporter mouse, aging cohort, bleomycin lung injury model, dasatinib+quercetin senolytic treatment, in vivo imaging

    PMID:36396643

    Open questions at the time
    • Whether GLB1 upregulation is a causal contributor to senescence phenotypes or purely a consequence remains unanswered
    • Mechanism of transcriptional/translational control of GLB1 during aging still unresolved

Open questions

Synthesis pass · forward-looking unresolved questions
  • The transcriptional and translational regulatory mechanisms that drive GLB1 upregulation during senescence and aging remain undefined, and whether elevated β-galactosidase activity plays a functional role in the senescent phenotype (beyond serving as a biomarker) is an open question.
  • No structural model of the full lysosomal multienzyme complex
  • Whether EBP splice-variant dysregulation contributes to age-related vascular pathology not tested
  • Functional consequence of elevated lysosomal β-galactosidase in senescent cells unknown

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0016787 hydrolase activity 3 GO:0098631 cell adhesion mediator activity 3
Localization
GO:0005764 lysosome 4 GO:0005886 plasma membrane 4
Pathway
R-HSA-1430728 Metabolism 3 R-HSA-1643685 Disease 3 R-HSA-1474244 Extracellular matrix organization 2 GO:0016787 hydrolase activity 1
Partners
CTSANEU1
Complex memberships
EBP cell-surface complex (67-kDa GLB1 splice variant–CTSA–NEU1)Lysosomal multienzyme complex (GLB1–CTSA–NEU1)

Evidence

Reading pass · 11 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
1968 Profound deficiency of β-galactosidase activity (failing to cleave both p-nitrophenyl-β-D-galactopyranoside and GM1 ganglioside labeled with C14) was identified in tissues of patients with generalized gangliosidosis, establishing that defective lysosomal β-galactosidase (GLB1) is the fundamental enzymatic defect responsible for GM1 ganglioside accumulation in this disease. Enzymatic activity assay on liver, spleen, kidney and brain tissue homogenates from patients Science High 5647842
1985 Lysosomal β-galactosidase exists as a high-density multimeric complex that associates with both a 32-kDa protective protein (CTSA/cathepsin A) and neuraminidase, and formation of this multiprotein complex is required for neuraminidase catalytic activity; absence of the protective protein in galactosialidosis explains the secondary neuraminidase deficiency in that disorder. β-galactosidase affinity chromatography, immunotitration with monospecific antibodies, sucrose density gradient centrifugation of human placental fractions European journal of biochemistry High 3922758
1993 An alternatively spliced, enzymatically inactive 67-kDa form of β-galactosidase (encoded by GLB1) was identified as immunologically and functionally similar to the 67-kDa cell-surface elastin/laminin-binding protein (EBP); a unique peptide (S-GAL) derived from the frameshift-generated sequence of this splice variant binds elastin and laminin but not fibronectin or collagens. Antibody raised to unique splice-variant peptide; Western blot; elastin and laminin affinity column binding assays; immunohistochemistry of aortic tissue The Journal of clinical investigation High 8383699
1998 The 67-kDa alternatively spliced variant of GLB1 (S-gal) was conclusively identified as the elastin/laminin-binding protein: full-length S-gal cDNA expressed in COS-1 cells and EBP-deficient smooth muscle cells produced a 67-kDa protein that localized to the cell surface, bound elastin, increased cell adhesion to elastin, and corrected impaired elastic fiber assembly in deficient cells. cDNA transfection, in vitro transcription/translation, elastin/laminin affinity chromatography, immunolocalization, cell adhesion assay, elastic fiber assembly assay in EBP-deficient smooth muscle cells The Journal of biological chemistry High 9497360
2005 The alternatively spliced 67-kDa EBP (GLB1 splice variant) forms a cell surface-targeted multiprotein complex with protective protein/cathepsin A and sialidase (neuraminidase-1); this complex facilitates elastic fiber assembly by enabling neuraminidase-1 to remove terminal sialic acids from microfibrillar glycoproteins, exposing galactosugars that interact with the galectin domain of EBP and trigger tropoelastin release and assembly. Co-immunoprecipitation, sialidase inhibitor treatment, neuraminidase-1 cDNA transduction of sialidosis/galactosialidosis patient fibroblasts, chick embryo elastogenesis assay, bacterial sialidase rescue experiment The Journal of biological chemistry High 16314420
2006 Senescence-associated β-galactosidase (SA-β-gal) activity detectable at pH 6.0 in senescent cells originates from GLB1, the gene encoding lysosomal β-D-galactosidase: fibroblasts from GM1-gangliosidosis patients (defective lysosomal β-galactosidase) and normal late-passage fibroblasts depleted of GLB1 mRNA by shRNA both failed to express SA-β-gal despite undergoing replicative senescence; SA-β-gal induction during senescence was due at least in part to increased GLB1 protein expression. shRNA knockdown of GLB1, SA-β-gal activity assay at pH 6.0, patient fibroblasts from GM1-gangliosidosis, HPV E7 repression-induced senescence model, Western blot Aging cell High 16626397
2010 Genotype-phenotype analysis of 28 GLB1 mutations in GM1 gangliosidosis patients revealed that overexpression of missense mutations in COS-1 cells and assessment of subcellular localization of mutant proteins in fibroblasts can predict phenotype specificity; mutations producing truncated proteins consistently result in typical CDPX2-like severe phenotype, while missense mutations show variable phenotypic outcomes, indicating that residual β-galactosidase enzyme activity correlates with clinical severity. Overexpression in COS-1 cells, immunofluorescence subcellular localization in patient fibroblasts, DNA sequencing, β-galactosidase enzyme activity assay Clinical genetics Medium 20175788
2011 An alternatively spliced form of GLB1 (the EBP splice variant) is present on human choroidal endothelial cells and acts as a cell-surface receptor for elastin-derived peptides (EDPs), mediating their pro-angiogenic effects; EDP-induced cell migration was blocked by inhibitors targeting EBP/GLB1 but not other EDP-binding proteins, and elevated circulating EDPs in vivo increased collagen IV expression and deposition in the RPE/choroid. RT-PCR for GLB1 isoform expression, cell migration assay with receptor-specific inhibitors, in vivo mouse EDP injection with electroretinography, transmission electron microscopy, and microarray analysis Matrix biology Medium 22178079
2015 GLB1 protein (lysosomal β-galactosidase) accumulates in replicative senescence and therapy-induced senescence in prostate epithelial cells and cancer lines, correlating with senescent morphology and p16/CDKN2A expression; in tissue microarrays, GLB1 expression is elevated in high-grade prostatic intraepithelial neoplasia and primary cancer compared with benign tissue, with senescent cells showing low Ki67 and elevated HP1γ. Immunofluorescent staining with new GLB1 antibody, automated quantitative imaging (AQUA and Vectra), replicative senescence passage assay in primary cultures, chemotherapy-induced senescence in PCa lines PloS one Medium 25876105
2019 CRISPR/Cas9 knockout of GLB1 in human iPSC-derived cerebral organoids caused progressive accumulation of GM1 ganglioside; microinjection of AAV9-GLB1 vector into these organoids significantly increased β-galactosidase activity and reduced GM1 ganglioside content, demonstrating that GLB1 gene delivery is sufficient to restore enzymatic function and reduce substrate storage in a human CNS model. CRISPR/Cas9 genome editing targeting GLB1 exons 2 and 6, cerebral organoid generation, β-galactosidase enzyme activity assay, GM1 ganglioside quantification, AAV9-GLB1 microinjection Molecular genetics and metabolism reports High 31534909
2022 A Glb1-2A-mCherry (GAC) knock-in reporter allele at the endogenous Glb1 locus in mice showed that GLB1/lysosomal β-galactosidase protein levels increase linearly with chronological age in middle-aged mice and are exponentially elevated in bleomycin-induced pathological senescence in the lung; treatment with senolytics dasatinib and quercetin reduced GAC signal in bleomycin-treated mice, confirming that GLB1 expression marks senescent cell burden in vivo. CRISPR knock-in reporter allele (Glb1-2A-mCherry), cohort aging study, bleomycin lung injury model, in vivo imaging, senolytic drug treatment Nature communications High 36396643

Source papers

Stage 0 corpus · 130 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
1991 Regulated expression of three C/EBP isoforms during adipose conversion of 3T3-L1 cells. Genes & development 1511 1840554
2002 Generation and initial analysis of more than 15,000 full-length human and mouse cDNA sequences. Proceedings of the National Academy of Sciences of the United States of America 1479 12477932
2006 Senescence-associated beta-galactosidase is lysosomal beta-galactosidase. Aging cell 1124 16626397
2015 The BioPlex Network: A Systematic Exploration of the Human Interactome. Cell 1118 26186194
2017 Architecture of the human interactome defines protein communities and disease networks. Nature 1085 28514442
2015 A human interactome in three quantitative dimensions organized by stoichiometries and abundances. Cell 1015 26496610
1988 Isolation of a recombinant copy of the gene encoding C/EBP. Genes & development 926 2850264
2002 Endothelial cell senescence in human atherosclerosis: role of telomere in endothelial dysfunction. Circulation 879 11927518
2020 A reference map of the human binary protein interactome. Nature 849 32296183
2007 Large-scale mapping of human protein-protein interactions by mass spectrometry. Molecular systems biology 733 17353931
2021 Dual proteome-scale networks reveal cell-specific remodeling of the human interactome. Cell 705 33961781
2008 PPARgamma and C/EBP factors orchestrate adipocyte biology via adjacent binding on a genome-wide scale. Genes & development 688 18981473
2011 Phylogenetic-based propagation of functional annotations within the Gene Ontology consortium. Briefings in bioinformatics 656 21873635
1989 The DNA binding domain of the rat liver nuclear protein C/EBP is bipartite. Science (New York, N.Y.) 611 2494700
2008 Large-scale proteomics and phosphoproteomics of urinary exosomes. Journal of the American Society of Nephrology : JASN 607 19056867
1996 Signals from the stressed endoplasmic reticulum induce C/EBP-homologous protein (CHOP/GADD153). Molecular and cellular biology 592 8754828
1995 Repression of the interleukin-6 promoter by estrogen receptor is mediated by NF-kappa B and C/EBP beta. Molecular and cellular biology 563 7651415
1994 Oligo-capping: a simple method to replace the cap structure of eukaryotic mRNAs with oligoribonucleotides. Gene 492 8125298
1995 Conditional ectopic expression of C/EBP beta in NIH-3T3 cells induces PPAR gamma and stimulates adipogenesis. Genes & development 456 7557387
2004 The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC). Genome research 438 15489334
2022 OpenCell: Endogenous tagging for the cartography of human cellular organization. Science (New York, N.Y.) 432 35271311
1968 Generalized gangliosidosis: beta-galactosidase deficiency. Science (New York, N.Y.) 421 5647842
2005 Diversification of transcriptional modulation: large-scale identification and characterization of putative alternative promoters of human genes. Genome research 409 16344560
1996 The human cytosolic molecular chaperones hsp90, hsp70 (hsc70) and hdj-1 have distinct roles in recognition of a non-native protein and protein refolding. The EMBO journal 357 8670798
1992 Differential expression of three C/EBP isoforms in multiple tissues during the acute phase response. The Journal of biological chemistry 280 1371993
2012 Genome-wide association study identifies eight new susceptibility loci for atopic dermatitis in the Japanese population. Nature genetics 278 23042114
2011 A directed protein interaction network for investigating intracellular signal transduction. Science signaling 258 21900206
1998 The t(8;21) fusion product, AML-1-ETO, associates with C/EBP-alpha, inhibits C/EBP-alpha-dependent transcription, and blocks granulocytic differentiation. Molecular and cellular biology 238 9418879
2005 Molecular stop signs: regulation of cell-cycle arrest by C/EBP transcription factors. Journal of cell science 237 15944395
1995 The C/EBP family of transcription factors. Immunobiology 220 8530141
2016 An organelle-specific protein landscape identifies novel diseases and molecular mechanisms. Nature communications 211 27173435
1996 C/EBP, c-Myb, and PU.1 cooperate to regulate the neutrophil elastase promoter. Molecular and cellular biology 208 8756629
2011 Toward an understanding of the protein interaction network of the human liver. Molecular systems biology 207 21988832
2008 GM1 gangliosidosis: review of clinical, molecular, and therapeutic aspects. Molecular genetics and metabolism 194 18524657
2013 C/EBP maintains chromatin accessibility in liver and facilitates glucocorticoid receptor recruitment to steroid response elements. The EMBO journal 188 23665916
2012 C/EBP transcription factors mediate epicardial activation during heart development and injury. Science (New York, N.Y.) 188 23160954
1997 CREB controls LAP/C/EBP beta transcription. Molecular and cellular biology 175 9199295
2014 Global mapping of herpesvirus-host protein complexes reveals a transcription strategy for late genes. Molecular cell 173 25544563
2002 An essential role for a MEK-C/EBP pathway during growth factor-regulated cortical neurogenesis. Neuron 170 12441050
2021 Senescence-associated β-galactosidase reveals the abundance of senescent CD8+ T cells in aging humans. Aging cell 164 33939265
2017 Transcription Factor C/EBP Homologous Protein in Health and Diseases. Frontiers in immunology 164 29230213
1994 C/EBP beta regulation of the tumor necrosis factor alpha gene. The Journal of clinical investigation 161 7929820
2010 Vitamin D suppresses Th17 cytokine production by inducing C/EBP homologous protein (CHOP) expression. The Journal of biological chemistry 158 20974859
2003 Dominant-negative C/EBP disrupts mitotic clonal expansion and differentiation of 3T3-L1 preadipocytes. Proceedings of the National Academy of Sciences of the United States of America 157 14688407
1993 The 67-kD elastin/laminin-binding protein is related to an enzymatically inactive, alternatively spliced form of beta-galactosidase. The Journal of clinical investigation 157 8383699
1998 The 67-kDa enzymatically inactive alternatively spliced variant of beta-galactosidase is identical to the elastin/laminin-binding protein. The Journal of biological chemistry 154 9497360
2001 Altered expression of C/EBP family members results in decreased adipogenesis with aging. American journal of physiology. Regulatory, integrative and comparative physiology 145 11353682
2013 In-depth proteomic analyses of exosomes isolated from expressed prostatic secretions in urine. Proteomics 138 23533145
1985 Human placental neuraminidase. Activation, stabilization and association with beta-galactosidase and its protective protein. European journal of biochemistry 134 3922758
2002 Mechanism of c-Myb-C/EBP beta cooperation from separated sites on a promoter. Cell 133 11792321
2005 Lysosomal sialidase (neuraminidase-1) is targeted to the cell surface in a multiprotein complex that facilitates elastic fiber assembly. The Journal of biological chemistry 130 16314420
2013 Proteomic analysis of podocyte exosome-enriched fraction from normal human urine. Journal of proteomics 126 23376485
1997 Cloning of the novel human myeloid-cell-specific C/EBP-epsilon transcription factor. Molecular and cellular biology 124 9032264
2012 C/EBP homologous protein contributes to cytokine-induced pro-inflammatory responses and apoptosis in β-cells. Cell death and differentiation 123 22653339
1991 DNA-induced increase in the alpha-helical content of C/EBP and GCN4. Biochemistry 114 1892816
2001 The role of C/EBP(epsilon) in the terminal stages of granulocyte differentiation. Stem cells (Dayton, Ohio) 110 11239167
1995 Ig/EBP (C/EBP gamma) is a transdominant negative inhibitor of C/EBP family transcriptional activators. Nucleic acids research 108 7501458
1998 The C/EBP family of transcription factors in the liver and other organs. International journal of experimental pathology 104 10319019
2020 JAM-A Acts via C/EBP-α to Promote Claudin-5 Expression and Enhance Endothelial Barrier Function. Circulation research 103 32673519
2000 C/EBP regulates hepatic transcription of 11beta -hydroxysteroid dehydrogenase type 1. A novel mechanism for cross-talk between the C/EBP and glucocorticoid signaling pathways. The Journal of biological chemistry 102 10906322
1996 C/EBP activators are required for HIV-1 replication and proviral induction in monocytic cell lines. Immunity 91 8758898
2011 IMiD immunomodulatory compounds block C/EBP{beta} translation through eIF4E down-regulation resulting in inhibition of MM. Blood 83 21389327
2002 Calreticulin interacts with C/EBPalpha and C/EBPbeta mRNAs and represses translation of C/EBP proteins. Molecular and cellular biology 81 12242300
2002 C/EBP DNA-binding activity is upregulated by a glucocorticoid-dependent mechanism in septic muscle. American journal of physiology. Regulatory, integrative and comparative physiology 74 11792653
1992 Drosophila C/EBP: a tissue-specific DNA-binding protein required for embryonic development. Genes & development 68 1459454
2011 C/EBP-δ regulates VEGF-C autocrine signaling in lymphangiogenesis and metastasis of lung cancer through HIF-1α. Oncogene 67 21666710
2007 The interferon signaling network and transcription factor C/EBP-beta. Cellular & molecular immunology 66 18163952
2015 Overexpression of the novel senescence marker β-galactosidase (GLB1) in prostate cancer predicts reduced PSA recurrence. PloS one 64 25876105
2013 C/EBP homologous protein drives pro-catabolic responses in chondrocytes. Arthritis research & therapy 62 24351550
2003 The Papillomavirus E2 protein binds to and synergizes with C/EBP factors involved in keratinocyte differentiation. Journal of virology 60 12692227
2002 Regulation of CCAAT/enhancer-binding protein (C/EBP) activator proteins by heterodimerization with C/EBPgamma (Ig/EBP). The Journal of biological chemistry 60 11980905
2000 Sp1 and C/EBP are necessary to activate the lactoferrin gene promoter during myeloid differentiation. Blood 60 10845904
2004 C/EBP beta isoforms LIP and LAP modulate progression of the cell cycle in the regenerating mouse liver. Hepatology (Baltimore, Md.) 59 15368440
1996 Induction of the C/EBP beta gene by dexamethasone and glucagon in primary-cultured rat hepatocytes. Journal of biochemistry 59 8830049
2008 Human C/EBP-epsilon activator and repressor isoforms differentially reprogram myeloid lineage commitment and differentiation. Blood 58 18832658
2019 Quercetin-Induced miR-369-3p Suppresses Chronic Inflammatory Response Targeting C/EBP-β. Molecular nutrition & food research 57 31338984
1996 A novel function for Myc: inhibition of C/EBP-dependent gene activation. Proceedings of the National Academy of Sciences of the United States of America 56 8692870
2000 Novel and recurrent EBP mutations in X-linked dominant chondrodysplasia punctata. American journal of medical genetics 54 11038443
2010 C/EBP-beta regulates endoplasmic reticulum stress-triggered cell death in mouse and human models. PloS one 52 20209087
2019 Human GLB1 knockout cerebral organoids: A model system for testing AAV9-mediated GLB1 gene therapy for reducing GM1 ganglioside storage in GM1 gangliosidosis. Molecular genetics and metabolism reports 50 31534909
2002 C/EBP-beta, C/EBP-delta, PU.1, AML1 genes: mutational analysis in 381 samples of hematopoietic and solid malignancies. Leukemia research 50 11916518
2001 Molecular cloning, genetic mapping, and expression analysis of four zebrafish c/ebp genes. Gene 50 11750126
1989 Molecular characterization of the major maize embryo globulin encoded by the glb1 gene. Plant physiology 50 16667080
2015 Endogenous prostaglandin E2 potentiates anti-inflammatory phenotype of macrophage through the CREB-C/EBP-β cascade. European journal of immunology 48 26118414
2003 Transcription cooperation by NFAT.C/EBP composite enhancer complex. The Journal of biological chemistry 48 12606546
1996 Control of adipocyte differentiation by CCAAT/enhancer binding protein alpha (C/EBP alpha). International journal of obesity and related metabolic disorders : journal of the International Association for the Study of Obesity 48 8680485
2017 Zinc transporter ZIP13 suppresses beige adipocyte biogenesis and energy expenditure by regulating C/EBP-β expression. PLoS genetics 46 28854265
2005 Cooperative interaction of C/EBP beta and Tat modulates MCP-1 gene transcription in astrocytes. Journal of neuroimmunology 46 15710476
2005 Myxoid liposarcoma FUS-DDIT3 fusion oncogene induces C/EBP beta-mediated interleukin 6 expression. International journal of cancer 45 15688424
2011 Stress-induced C/EBP homology protein (CHOP) represses MyoD transcription to delay myoblast differentiation. PloS one 44 22242125
2001 C/EBP epsilon mediates myeloid differentiation and is regulated by the CCAAT displacement protein (CDP/cut). Proceedings of the National Academy of Sciences of the United States of America 44 11438745
2015 The role of C/EBP-β LIP in multidrug resistance. Journal of the National Cancer Institute 42 25766403
2012 Inhibition of CD200R1 expression by C/EBP β in reactive microglial cells. Journal of neuroinflammation 42 22776069
2006 Fibrates upregulate TRB3 in lymphocytes independent of PPAR alpha by augmenting CCAAT/enhancer-binding protein beta (C/EBP beta) expression. Molecular immunology 42 16949670
2020 C/EBPɑ is crucial determinant of epithelial maintenance by preventing epithelial-to-mesenchymal transition. Nature communications 41 32034145
1993 Differential adrenergic regulation of C/EBP alpha and C/EBP beta in brown adipose tissue. FEBS letters 41 8440378
2003 RUNX/AML and C/EBP factors regulate CD11a integrin expression in myeloid cells through overlapping regulatory elements. Blood 40 12855590
2014 miRNA-130a regulates C/EBP-ε expression during granulopoiesis. Blood 39 24398327
2003 Regulation of Bcl-2 expression by C/EBP in t(14;18) lymphoma cells. Oncogene 37 12970736
2002 Macrophage functional maturation and cytokine production are impaired in C/EBP epsilon-deficient mice. Blood 37 11861297
2002 Interaction between TGFbeta signaling proteins and C/EBP controls basal and Tat-mediated transcription of HIV-1 LTR in astrocytes. Virology 37 12202226
2013 Reciprocal modulation of C/EBP-α and C/EBP-β by IL-13 in activated microglia prevents neuronal death. European journal of immunology 36 23881867
2020 Roles of C/EBP class bZip proteins in the growth and cell competition of Rp ('Minute') mutants in Drosophila. eLife 35 31909714
2013 Ablation of C/EBP homologous protein does not protect T17M RHO mice from retinal degeneration. PloS one 35 23646198
2004 Identification of murine and human XCP1 genes as C/EBP-epsilon-dependent members of FIZZ/Resistin gene family. Oncogene 35 15064728
2004 Suppression of C/EBP alpha expression in biliary cell differentiation from hepatoblasts during mouse liver development. Journal of hepatology 34 15519652
2022 A Glb1-2A-mCherry reporter monitors systemic aging and predicts lifespan in middle-aged mice. Nature communications 33 36396643
2015 XBP1-Independent UPR Pathways Suppress C/EBP-β Mediated Chondrocyte Differentiation in ER-Stress Related Skeletal Disease. PLoS genetics 33 26372225
2007 C/EBP homologous protein is crucial for the acceleration of experimental pancreatitis. Biochemical and biophysical research communications 33 18166146
2006 C/EBP homologous protein is necessary for normal osteoblastic function. Journal of cellular biochemistry 33 16220546
2018 Loss of C/EBP-β LIP drives cisplatin resistance in malignant pleural mesothelioma. Lung cancer (Amsterdam, Netherlands) 32 29748013
1993 The human C/EBP delta (CRP3/CELF) gene: structure and chromosomal localization. Genomics 32 8314590
2018 Ablation of C/EBP homologous protein attenuates renal fibrosis after ureteral obstruction by reducing autophagy and microtubule disruption. Biochimica et biophysica acta. Molecular basis of disease 31 29425932
2014 Mmu-miR-615-3p regulates lipoapoptosis by inhibiting C/EBP homologous protein. PloS one 31 25314137
2010 Phenotype determining alleles in GM1 gangliosidosis patients bearing novel GLB1 mutations. Clinical genetics 31 20175788
2010 C/EBP{delta} and STAT-1 are required for TLR8 transcriptional activity. The Journal of biological chemistry 31 20829351
2016 Coordinated inhibition of C/EBP by Tribbles in multiple tissues is essential for Caenorhabditis elegans development. BMC biology 30 27927209
2011 Molecular responses of choroidal endothelial cells to elastin derived peptides through the elastin-binding protein (GLB1). Matrix biology : journal of the International Society for Matrix Biology 30 22178079
2012 Artemisinic acid is a regulator of adipocyte differentiation and C/EBP δ expression. Journal of cellular biochemistry 28 22396222
2011 Role of C/EBP-β, p38 MAPK, and MKK6 in IL-1β-mediated C3 gene regulation in astrocytes. Journal of cellular biochemistry 27 21308746
2018 Impaired DNA demethylation of C/EBP sites causes premature aging. Genes & development 26 29884649
2014 C/EBP homologous protein inhibits tissue repair in response to gut injury and is inversely regulated with chronic inflammation. Mucosal immunology 26 24850428
2011 C/EBP-α and C/EBP-β-mediated adipogenesis of human mesenchymal stem cells (hMSCs) using PLGA nanoparticles complexed with poly(ethyleneimmine). Biomaterials 26 21600648
2009 Cyclic regulation of transcription factor C/EBP beta in human endometrium. Reproductive biology and endocrinology : RB&E 25 19222842
2003 Cloning of an emopamil-binding protein (EBP)-like protein that lacks sterol delta8-delta7 isomerase activity. The Biochemical journal 25 12760743
2013 The kinase domain of Drosophila Tribbles is required for turnover of fly C/EBP during cell migration. Developmental biology 24 23305818
2008 Sumoylation and the function of CCAAT enhancer binding protein alpha (C/EBP alpha). Blood cells, molecules & diseases 24 18406180
2016 Role of C/EBP-α in Adriamycin-induced podocyte injury. Scientific reports 23 27644413
2010 C/EBP alpha expression is associated with homeostasis of the gastric epithelium and with gastric carcinogenesis. Laboratory investigation; a journal of technical methods and pathology 23 20386538
2000 Regulation of Gadd45gamma expression by C/EBP. European journal of biochemistry 23 11012671