Affinage

MIB1

E3 ubiquitin-protein ligase MIB1 · UniProt Q86YT6

Length
1006 aa
Mass
110.1 kDa
Annotated
2026-06-10
100 papers in source corpus 15 papers cited in narrative 15 extracted findings
Cross-family judge vs UniProt: Affinage preferred faithfulness: 7/7 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

MIB1 is a RING-finger E3 ubiquitin ligase whose best-established role is to drive Notch signaling by ubiquitinating Notch ligands and promoting their endocytosis in signal-sending cells (PMID:23314057, PMID:17196985). It functions as a dimer, and its C-terminal RING finger is the catalytic domain: missense or truncation mutations there abolish ubiquitylation and ligand internalization (PMID:23314057, PMID:17196985). MIB1 ubiquitinates DELTA/DLL and JAGGED ligands, and at DLL1 it couples ligand ubiquitination to endocytosis by promoting a ubiquitin-ligase-activity-dependent interaction between dynamin 2 and Snx18, with ligase activity itself induced by ligand–receptor engagement (PMID:26923255). Through this activity MIB1 acts upstream of Notch1 in multiple developmental contexts, including cardiac trabecular compaction, spinal progenitor maintenance and interneuron/glial specification, and Notch-dependent angiogenic tip-cell behavior, the last regulated by miR-10a/10b repression of mib1 (PMID:23314057, PMID:23223237, PMID:26825552). Loss-of-function MIB1 mutations that impair dimerization or ligand ubiquitination cause left ventricular noncompaction cardiomyopathy and, on a NOTCH1-sensitized background, bicuspid aortic valve, establishing MIB1 as a Notch-pathway disease gene in cardiogenesis (PMID:23314057, PMID:30322850, PMID:37405741). Beyond Notch, MIB1 has substrate-specific roles in centrosome and satellite biology—ubiquitinating Plk4 with K11/K29/K48 chains to restrain centriole amplification, and marking PCM1 for proteasomal degradation, an action opposed by the deubiquitinases CYLD and the SNX17–USP9X complex during ciliogenesis (PMID:25795303, PMID:31067453, PMID:31671755)—and it directs persistent directional migration by ubiquitinating Ctnnd1 (p120-catenin) on K547 to dampen Rac1 activity (PMID:29078376). In cancer cells MIB1 promotes proliferation by targeting the tumor suppressors ST7 and DAPK1, and the topoisomerase TOP3B, for proteasomal degradation (PMID:33793053, PMID:37346933, PMID:37980342).

Mechanistic history

Synthesis pass · year-by-year structured walk · 13 steps
  1. 2006 High

    Established that the C-terminal RING finger is MIB1's catalytic domain, answering whether MIB1 is intrinsically an E3 ligase and which domain executes ligand ubiquitination and internalization.

    Evidence In vitro ubiquitylation assays with RING-domain point/truncation mutants and Delta internalization assays in zebrafish Mib/Mib2

    PMID:17196985

    Open questions at the time
    • Cognate E2 enzyme(s) not defined
    • Chain linkage types on Delta substrates not mapped
  2. 2012 High

    Showed the RING-dependent ligase activity is required in vivo for Notch ligand function during neural development, linking MIB1 catalysis to progenitor maintenance and cell-fate specification.

    Evidence Conditional/inducible Mib1 knockout mouse and chick neural tube misexpression of RING-deletion mutants

    PMID:23223237

    Open questions at the time
    • Which ligand substrate is most relevant in spinal cord not resolved
    • Direct substrate ubiquitination not measured in this system
  3. 2013 High

    Demonstrated MIB1 acts as a dimer upstream of Notch1 in heart development and that human loss-of-function mutations disrupting dimerization cause cardiomyopathy, connecting MIB1 biochemistry to Mendelian disease.

    Evidence Mouse conditional knockouts with genetic epistasis, zebrafish studies, in silico dimer modeling, and human pedigree sequencing

    PMID:23314057

    Open questions at the time
    • Structural basis of dimerization not solved
    • Direct ligand ubiquitination by mutant proteins not quantified here
  4. 2015 High

    Identified a Notch-independent substrate, showing MIB1 ubiquitinates Plk4 with K11/K29/K48 chains to limit centriole amplification and localizes to centriolar satellites.

    Evidence Co-IP, MS-mapped ubiquitin linkages, immunofluorescence localization, and centriole amplification assays

    PMID:25795303

    Open questions at the time
    • Fate of Plk4 (degradation vs. signaling) per linkage type not fully separated
    • Regulation of MIB1 redistribution to centrioles unknown
  5. 2016 Medium

    Defined how MIB1 couples ligand ubiquitination to endocytosis and how its activity is regulated, showing ligand–receptor engagement induces MIB1 activity that promotes dynamin 2–Snx18 interaction for Dll1 internalization.

    Evidence Co-IP interaction mapping, ligase activity assays, and Dll1 endocytosis assays with dominant-negative dynamin 2 and Snx18 knockdown

    PMID:26923255

    Open questions at the time
    • Snx18 contribution is modest and mechanism partial
    • Direct ubiquitination of dynamin 2 vs. ligand not separated
  6. 2016 Medium

    Placed mib1 under post-transcriptional control, showing miR-10a/10b represses mib1 to tune Notch-dependent angiogenic tip-cell behavior.

    Evidence Luciferase 3'-UTR reporter, zebrafish in vivo reporter, morpholino knockdown, and Mib1/Notch rescue epistasis

    PMID:26825552

    Open questions at the time
    • Whether this regulation operates in mammalian angiogenesis not shown
    • Quantitative contribution to endogenous MIB1 levels unclear
  7. 2017 High

    Extended MIB1's function beyond Notch to cell migration, identifying Ctnnd1 K547 ubiquitination as a brake on Rac1 that enforces persistent directional migration.

    Evidence Ubiquitination site mutagenesis, Rac1 activity assay, wound-closure migration, and zebrafish lateral-line rescue with Ctnnd1 morpholino

    PMID:29078376

    Open questions at the time
    • Whether K547 ubiquitination is degradative or non-degradative not stated
    • Molecular link between ubiquitinated Ctnnd1 and Rac1 suppression undefined
  8. 2018 Medium

    Provided patient-derived biochemical confirmation that disease mutations impair JAG1 ubiquitination, reinforcing that MIB1 ligase activity toward JAG1 drives cardiogenic Notch activation.

    Evidence In-cell JAG1 ubiquitination assays comparing mutant vs. wild-type MIB1 plus Notch reporter

    PMID:30322850

    Open questions at the time
    • Single-lab cell-based assay without in vivo validation in this study
    • Effect on other ligands not tested
  9. 2019 Medium

    Revealed that MIB1's ubiquitination of PCM1 is reversed by deubiquitinases, defining CYLD and the SNX17–USP9X complex as antagonists that protect centriolar satellites during ciliogenesis.

    Evidence Proteomic screens, Co-IP, CYLD/SNX17 knockdown with PCM1 (and USP9X) degradation readouts, and ciliogenesis assays

    PMID:31067453 PMID:31671755

    Open questions at the time
    • PCM1 ubiquitination site(s) and chain type not mapped
    • How serum starvation switches SNX17 dependence not explained
  10. 2019 Medium

    Linked MIB1 to cancer proliferation, showing miR-198 represses MIB1 and that MIB1 knockdown phenocopies miR-198 anti-proliferative effects in prostate cancer.

    Evidence 3'-UTR luciferase reporter, miR-198 mimic, MIB1 siRNA, and LNCaP xenografts

    PMID:31322262

    Open questions at the time
    • Relevant MIB1 substrate driving prostate proliferation not identified
    • Single-lab study
  11. 2021 Medium

    Identified an oncogenic MIB1 substrate axis, showing MIB1 degrades the tumor suppressor ST7 to upregulate IQGAP1 and promote pancreatic cancer proliferation and invasion.

    Evidence Overexpression/knockdown in pancreatic cancer cells, Co-IP, proteasome-inhibitor rescue, and xenografts

    PMID:33793053

    Open questions at the time
    • ST7 ubiquitination site not mapped
    • Generality across tumor types not tested
  12. 2023 Medium

    Expanded MIB1's substrate repertoire to TOP3B and DAPK1, defining MIB1 as the E3 ligase degrading these proteins, with TDRD3–USP9X stabilizing TOP3B downstream and DAPK1 degradation underlying GBM proliferation.

    Evidence Co-IP, triple-knockdown epistasis for TOP3B; protein-stability and rescue assays plus GBM proliferation/apoptosis models for DAPK1

    PMID:37346933 PMID:37980342

    Open questions at the time
    • Ubiquitination sites on TOP3B and DAPK1 not mapped
    • Single-lab studies, chain linkage types undefined
  13. 2023 High

    Causally tied MIB1 loss-of-function to bicuspid aortic valve through Notch, demonstrating in vivo disease mechanism on a NOTCH1-sensitized background.

    Evidence Two genetically modified mouse models with human MIB1 variants on NOTCH1-sensitized background and multicenter human familial exome replication

    PMID:37405741

    Open questions at the time
    • Cell type and developmental window of the critical Notch defect not pinpointed
    • Variant-specific biochemical effects not all characterized

Open questions

Synthesis pass · forward-looking unresolved questions
  • How MIB1 substrate selection is partitioned between Notch ligands and its many non-Notch targets (Plk4, PCM1, Ctnnd1, ST7, DAPK1, TOP3B), and which ubiquitin chain linkages dictate degradation versus trafficking, remains unresolved.
  • No structural model of MIB1 substrate recognition
  • Cognate E2 enzymes not defined across substrates
  • Chain-linkage-to-fate rules characterized only for Plk4

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0140096 catalytic activity, acting on a protein 6 GO:0016874 ligase activity 5
Localization
GO:0005815 microtubule organizing center 1
Pathway
R-HSA-392499 Metabolism of proteins 5 R-HSA-1266738 Developmental Biology 4 R-HSA-162582 Signal Transduction 4 R-HSA-1643685 Disease 4

Evidence

Reading pass · 15 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2013 MIB1 functions as a dimer to promote endocytosis of NOTCH ligands DELTA and JAGGED (E3 ubiquitin ligase activity); germline loss-of-function mutations disrupt dimerization, reduce NOTCH1 activity, and cause left ventricular noncompaction cardiomyopathy. Targeted inactivation of Mib1 in mouse myocardium phenocopies inactivation of myocardial Jagged1 or endocardial Notch1, placing Mib1 upstream of Notch1 in cardiac trabecular compaction. Genetic epistasis in mouse conditional knockouts, zebrafish functional studies, in silico modeling, human pedigree sequencing with reduced NOTCH1 target gene expression Nature medicine High 23314057
2006 Zebrafish Mib and Mib2 both possess C-terminal RING finger-dependent E3 ubiquitin ligase activity and are reciprocal E3 ubiquitin ligases and substrates of each other. They share DeltaC as a common substrate but differ in DeltaD internalization. Dominant-negative missense (M1013R) or truncation (C785stop) mutations in the C-terminal RING finger abolish ubiquitylation and internalization of DeltaC, establishing the RING finger as the catalytic domain. In vitro ubiquitylation assays, site-directed mutagenesis of RING finger domain, Delta internalization assays Journal of molecular biology High 17196985
2012 Mib1 E3 ubiquitin ligase is required for Notch ligand activity in the developing spinal cord: conditional knockout mice show depletion of spinal progenitors, premature neuronal differentiation, unbalanced V2 interneuron specification, and loss of astrocytes/oligodendrocytes. The RING domain of Mib1 is required for V2 interneuron specification in chick neural tube, established by misexpression of RING-domain deletion mutants. Conditional knockout mouse, drug-inducible deletion, chick neural tube misexpression of Mib1 deletion mutants The Journal of biological chemistry High 23223237
2015 Mib1 interacts with Polo-like kinase 4 (Plk4) and ubiquitylates Plk4 on multiple sites, generating Lys11-, Lys29-, and Lys48-linked ubiquitin chains. This controls Plk4 abundance and its interaction with centrosomal proteins, thereby counteracting centriole amplification. Mib1 localizes to centriolar satellites and redistributes to centrioles upon conditions that induce centriole amplification. Co-immunoprecipitation, mass spectrometry-identified interaction, ubiquitylation assay with linkage-type mapping, subcellular localization by immunofluorescence, gain-of-function centriole amplification assay Journal of cell science High 25795303
2019 The deubiquitinase CYLD antagonizes MIB1 by removing ubiquitin from PCM1 (pericentriolar material protein 1), preventing MIB1-mediated proteasomal degradation of PCM1. Loss of CYLD leads to PCM1 degradation and dismantling of centriolar satellites, disrupting ciliogenesis. Thus MIB1 marks PCM1 for proteasomal degradation, and CYLD reverses this modification. Proteomic screen for CYLD binding partners, CYLD knockdown with PCM1 degradation readout, co-immunoprecipitation, centriolar satellite and ciliogenesis assays Cell reports High 31067453
2019 SNX17 recruits the deubiquitinase USP9X to antagonize MIB1-induced ubiquitination and proteasomal degradation of PCM1 during serum-starvation-induced ciliogenesis. SNX17 deficiency enhances PCM1 and USP9X degradation and disrupts ciliogenesis. Under serum-containing conditions, SNX17 is dispensable for PCM1/USP9X homeostasis. Co-immunoprecipitation, knockdown of SNX17 with PCM1/USP9X degradation readout, ciliogenesis assay under serum starvation vs. normal conditions Cells Medium 31671755
2016 miR-10a/10b directly binds the 3′-UTR of mib1 mRNA and represses its expression in endothelial cells. Loss of miR-10a/10b increases Mib1, impairs tip-cell behavior, and disrupts angiogenesis in a Notch-dependent manner; inhibition of Mib1 or Notch signaling rescues the angiogenic defects in miR-10-deficient zebrafish. Luciferase 3′-UTR reporter assay, in vivo zebrafish reporter assay, morpholino knockdown, epistasis with Mib1/Notch inhibition rescue Cardiovascular research Medium 26825552
2017 Mib1 ubiquitinates Ctnnd1 (p120-catenin) on K547, and this ubiquitination attenuates Rac1 activation. Loss of Mib1 increases random cell migration due to hyperactivated Rac1; knockdown of Ctnnd1 partially rescues posterior lateral line primordium migration defects in mib1 zebrafish mutants, placing the Mib1–Ctnnd1–Rac1 axis in persistent directional cell migration. siRNA knockdown in wound-closure assay, ubiquitination site mutagenesis (K547), Rac1 activity assay, zebrafish mib1 mutant lateral line analysis with Ctnnd1 morpholino rescue Proceedings of the National Academy of Sciences of the United States of America High 29078376
2016 Mib1 promotes Notch ligand Dll1 endocytosis by modulating dynamin 2 recruitment: Mib1 promotes the interaction between dynamin 2 and Snx18 in a ubiquitin ligase activity-dependent manner. Mib1 ubiquitin ligase activity is induced by Notch ligand–receptor interactions. Snx18 modestly regulates Dll1 endocytosis. Co-immunoprecipitation, ubiquitin ligase activity assay, Dll1 endocytosis assay, dominant-negative dynamin 2 and Snx18 knockdown Genes to cells : devoted to molecular & cellular mechanisms Medium 26923255
2021 MIB1 directly targets the tumor suppressor ST7 for proteasomal degradation via ubiquitination. ST7 suppresses tumor growth by downregulating IQGAP1. MIB1 overexpression in pancreatic cancer cells enhances proliferation and invasion by degrading ST7, leading to upregulation of IQGAP1, defining a MIB1/ST7/IQGAP1 oncogenic axis. Overexpression and knockdown in pancreatic cancer cells, in vitro and xenograft proliferation/invasion assays, co-immunoprecipitation, proteasome inhibitor rescue Molecular oncology Medium 33793053
2023 MIB1 mediates ubiquitination and proteasomal degradation of TOP3B by directly interacting with TOP3B independently of TDRD3. The TDRD3–USP9X complex works downstream of MIB1 to stabilize TOP3B; combined depletion of USP9X, TDRD3, and MIB1 does not increase TOP3B levels beyond MIB1 knockdown alone. Co-immunoprecipitation, USP9X/MIB1 knockdown with TOP3B ubiquitylation and stability readout, epistasis by combined depletion Nature communications Medium 37980342
2018 MIB1 mutations identified in congenital heart disease patients (p.T312Kfs*55 and p.W271G) significantly reduce JAGGED1 ubiquitination and Notch signaling induction in cell-based assays, demonstrating that MIB1 E3 ligase activity toward JAG1 is required for Notch pathway activation in cardiogenesis. Biochemical ubiquitination assays of JAG1 by mutant vs. wild-type MIB1 in transfected cells, Notch signaling reporter assay Clinical science (London, England : 1979) Medium 30322850
2023 MIB1 variants identified in familial nonsyndromic bicuspid aortic valve (nsBAV) pedigrees cause BAV on a NOTCH1-sensitized genetic background in two genetically modified mouse models, confirming that MIB1 loss-of-function is causally linked to BAV through reduced Notch pathway activation. Genetically modified mouse models carrying human MIB1 variants, NOTCH1-sensitized background epistasis, human familial exome sequencing with replication cohorts JAMA cardiology High 37405741
2023 MIB1 ubiquitinates and promotes proteasomal degradation of DAPK1; the flavonoid Sanggenon C suppresses GBM cell proliferation by decreasing MIB1 expression, thereby stabilizing DAPK1. Overexpression of MIB1 or knockdown of DAPK1 reverses the anti-proliferative effects, establishing MIB1 as the E3 ligase responsible for DAPK1 degradation. Western blot proteomic analysis, MIB1 overexpression/knockdown, DAPK1 stability assays, in vitro and in vivo GBM proliferation/apoptosis assays MedComm Medium 37346933
2019 MIB1 is a direct target of miR-198 in prostate cancer; miR-198 overexpression reduces MIB1 protein/mRNA, and MIB1 knockdown recapitulates the anti-proliferative effects of miR-198 (reduced colony formation, G0/G1 arrest, impaired in vivo tumor formation), demonstrating that MIB1 promotes prostate cancer cell proliferation downstream of miR-198. Luciferase 3′-UTR reporter assay, miR-198 mimic transfection, siRNA knockdown of MIB1, LNCaP xenograft model Oncology reports Medium 31322262

Source papers

Stage 0 corpus · 100 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2013 Mutations in the NOTCH pathway regulator MIB1 cause left ventricular noncompaction cardiomyopathy. Nature medicine 277 23314057
2016 MIB: Metal Ion-Binding Site Prediction and Docking Server. Journal of chemical information and modeling 197 27976886
2002 Correlation between MIB-1 and other proliferation markers: clinical implications of the MIB-1 cutoff value. Cancer 151 12001111
2012 Interplay among BRAF, p16, p53, and MIB1 in pediatric low-grade gliomas. Neuro-oncology 114 22492957
1994 MIB1 staining index and scoring of histologic features in meningioma. Indicators for the prediction of biologic potential and postoperative management. Cancer 109 7982181
2001 MIB-1 (Ki-67), p53, estrogen receptor, and progesterone receptor expression in uterine smooth muscle tumors. Human pathology 106 11567229
2000 Paraffin section storage and immunohistochemistry. Effects of time, temperature, fixation, and retrieval protocol with emphasis on p53 protein and MIB1 antigen. Applied immunohistochemistry & molecular morphology : AIMM 101 10937051
2000 Cell membrane and cytoplasmic staining for MIB-1 in hyalinizing trabecular adenoma of the thyroid gland. The American journal of surgical pathology 79 10757406
1998 MIB-1 labeling indices in benign, aggressive, and malignant meningiomas: a study of 90 tumors. Human pathology 73 9865827
2002 Microvessel density, expression of estrogen receptor alpha, MIB-1, p53, and c-erbB-2 in inflammatory breast cancer. Clinical cancer research : an official journal of the American Association for Cancer Research 68 12473600
2016 MIB-MIP is a mycoplasma system that captures and cleaves immunoglobulin G. Proceedings of the National Academy of Sciences of the United States of America 67 27114507
2008 Biomarker (ProEx C, p16(INK4A), and MiB-1) distinction of high-grade squamous intraepithelial lesion from its mimics. Modern pathology : an official journal of the United States and Canadian Academy of Pathology, Inc 67 18552822
2014 Prostate cancer Ki-67 (MIB-1) expression, perineural invasion, and gleason score as biopsy-based predictors of prostate cancer mortality: the Mayo model. Mayo Clinic proceedings 66 24486077
1999 Histopathologic features and MIB-1 labeling indices in recurrent and nonrecurrent meningiomas. Archives of pathology & laboratory medicine 66 10458826
1994 MIB-1, Ki67, and PCNA scores and DNA flow cytometry in intermediate grade malignant lymphomas. Journal of clinical pathology 65 7907607
2007 Poly(adenosine diphosphate-ribose) polymerase expression in serous ovarian carcinoma: correlation with p53, MIB-1, and outcome. International journal of gynecological pathology : official journal of the International Society of Gynecological Pathologists 61 17413981
1998 The relationship between MIB-1 proliferation index and outcome in pancreatic neuroendocrine tumors. American journal of clinical pathology 60 9495200
2003 P53 and MIB-1 immunohistochemistry as predictors of the clinical behavior of nonfunctioning pituitary adenomas. The Canadian journal of neurological sciences. Le journal canadien des sciences neurologiques 59 12945944
1996 Viral and histopathologic correlates of MN and MIB-1 expression in cervical intraepithelial neoplasia. Human pathology 59 8600036
2016 MicroRNA-10a/10b represses a novel target gene mib1 to regulate angiogenesis. Cardiovascular research 57 26825552
2007 Cell membrane reactivity of MIB-1 antibody to Ki67 in human tumors: fact or artifact? Applied immunohistochemistry & molecular morphology : AIMM 57 17525638
2015 The E3 ubiquitin ligase Mib1 regulates Plk4 and centriole biogenesis. Journal of cell science 56 25795303
2005 Immunohistochemical expression of p63, p53 and MIB-1 in urinary bladder carcinoma. A tissue microarray study of 158 cases. Virchows Archiv : an international journal of pathology 50 16283378
2012 The E3 ligase Mind bomb-1 (Mib1) modulates Delta-Notch signaling to control neurogenesis and gliogenesis in the developing spinal cord. The Journal of biological chemistry 41 23223237
2004 Expression of cell proliferation markers in pituitary adenomas--correlation and clinical relevance of MIB-1 and anti-topoisomerase-IIalpha. Acta neurochirurgica 41 15254805
2006 Correlation of p53 and MIB-1 expression with both the systemic recurrence and survival in cases of phyllodes tumors of the breast. Pathology, research and practice 40 16889904
2004 PTEN gene mutation and high MIB-1 labeling index may contribute to dissemination in patients with glioblastoma. Journal of clinical neuroscience : official journal of the Neurosurgical Society of Australasia 39 14642363
2003 MIB-1 and DNA topoisomerase II alpha could be helpful for predicting long-term survival of patients with glioblastoma. American journal of clinical pathology 39 12760291
1995 Expression of a cell-cycle-associated nuclear antigen (MIB 1) in cholesteatoma and auditory meatal skin. The Laryngoscope 37 7475881
2016 Removal of 2-MIB and geosmin by electrogenerated persulfate: Performance, mechanism and pathways. Chemosphere 36 27914726
2007 MIB-1 immunolabeling: a valuable marker in prediction of benign recurring meningiomas. Neuropathology : official journal of the Japanese Society of Neuropathology 36 18018472
2011 Giant pituitary adenomas: pathologic-radiographic correlations and lack of role for p53 and MIB-1 labeling. The American journal of surgical pathology 35 21753697
2006 Zebrafish Mib and Mib2 are mutual E3 ubiquitin ligases with common and specific delta substrates. Journal of molecular biology 34 17196985
2005 Correlation between histological grade and MIB-1 and p53 immunoreactivity in meningiomas. Clinical neuropathology 34 16167545
1998 Cell proliferation rate by MIB-1 immunohistochemistry predicts postradiation recurrence in prostatic adenocarcinomas. American journal of clinical pathology 34 9583887
1997 Comparison of quantitative and semiquantitative methods of assessing MIB-1 with the S-phase fraction in breast carcinoma. Modern pathology : an official journal of the United States and Canadian Academy of Pathology, Inc 34 9267818
2005 Expression of cell cycle-regulatory proteins, MIB-1, p16, p53, and p63, in squamous cell carcinoma of conjunctiva: not associated with human papillomavirus infection. Virchows Archiv : an international journal of pathology 32 16328355
2017 Parafibromin, APC, and MIB-1 Are Useful Markers for Distinguishing Parathyroid Carcinomas From Adenomas. Applied immunohistochemistry & molecular morphology : AIMM 30 27490759
2014 An analysis of granulation patterns, MIB-1 proliferation indices and p53 expression in 101 patients with acromegaly. Acta neurochirurgica 30 25238988
2019 CYLD Regulates Centriolar Satellites Proteostasis by Counteracting the E3 Ligase MIB1. Cell reports 29 31067453
2000 Endocervical intraepithelial glandular atypia (dysplasia): a histopathologic, human papillomavirus, and MIB-1 analysis of 25 cases. Human pathology 29 10872657
1998 Bcl-2, p53 and MIB-1 expression in normal and neoplastic parathyroid tissues. Journal of endocrinological investigation 29 9591207
1999 Utility of proliferation-associated marker MIB-1 in evaluating lesions of the uterine cervix. Advances in anatomic pathology 28 10410171
1999 Immunohistochemical study of MIB1 expression in phyllodes tumor and fibroadenoma. Pathology international 28 10504552
2005 p27(kip1) and Ki-67 (MIB1) immunohistochemical expression in radical prostatectomy specimens of patients with clinically localized prostate cancer. In vivo (Athens, Greece) 27 16097446
1998 Cyclin A and MIB1 (Ki67) as markers of proliferative activity in primary renal neoplasms. Modern pathology : an official journal of the United States and Canadian Academy of Pathology, Inc 27 9796723
2010 Classifying B-cell non-Hodgkin lymphoma by using MIB-1 proliferative index in fine-needle aspirates. Cancer cytopathology 26 20544708
1996 Proliferation index determined by MIB-1 and recurrence in endometrial cancer. Gynecologic oncology 26 8641618
1994 Expression of MIB-1 (paraffin ki-67) and AgNOR morphology in endometrial adenocarcinomas of endometrioid type. International journal of gynecological pathology : official journal of the International Society of Gynecological Pathologists 26 8112955
2021 MIB1 upregulates IQGAP1 and promotes pancreatic cancer progression by inducing ST7 degradation. Molecular oncology 25 33793053
1997 Subependymal giant cell astrocytoma: a clinicopathologic study with HMB45 and MIB-1 immunohistochemical analysis. Modern pathology : an official journal of the United States and Canadian Academy of Pathology, Inc 25 9110292
1997 MIB-1 and S-phase cell fraction predict survival in non-Hodgkin's lymphomas. Cell proliferation 25 9332493
2017 Mib1 contributes to persistent directional cell migration by regulating the Ctnnd1-Rac1 pathway. Proceedings of the National Academy of Sciences of the United States of America 24 29078376
1999 MIB-1 expression is useful in distinguishing dysplasia from atrophy in elderly women. International journal of gynecological pathology : official journal of the International Society of Gynecological Pathologists 24 10202668
2001 Telomerase activity, MIB-1, PCNA, HPV 16 and p53 as diagnostic markers for cervical intraepithelial neoplasia. APMIS : acta pathologica, microbiologica, et immunologica Scandinavica 23 11878714
1998 Cell proliferation measured by MIB1 and timing of surgery for breast cancer. British journal of cancer 23 9652769
1997 Expression of telomerase RNA component correlates with the MIB-1 proliferation index in ependymomas. Journal of neuropathology and experimental neurology 23 9329458
2001 Combined analysis of MIB-1 and thyroid transcription factor-1 predicts survival in non-small cell lung carcinomas. Cancer letters 22 11121867
1998 Cyclin D1 and MIB-1 immunohistochemistry in pilocytic astrocytomas: a study of 48 cases. Human pathology 22 9865840
1997 Human telomerase RNA expression and MIB-1 (Ki-67) proliferation index distinguish hemangioblastomas from metastatic renal cell carcinomas. Journal of neuropathology and experimental neurology 22 9413283
1996 Comparison of p53 and MIB1 expression in benign and borderline areas of ovarian serous tumors. International journal of gynecological pathology : official journal of the International Society of Gynecological Pathologists 22 8852445
2019 SNX17 Recruits USP9X to Antagonize MIB1-Mediated Ubiquitination and Degradation of PCM1 during Serum-Starvation-Induced Ciliogenesis. Cells 21 31671755
2015 EZH2 expression in gliomas: Correlation with CDKN2A gene deletion/ p16 loss and MIB-1 proliferation index. Neuropathology : official journal of the Japanese Society of Neuropathology 21 26096306
2009 Impact of morphology, MIB-1, p53 and MGMT on outcome in pilocytic astrocytomas. Brain pathology (Zurich, Switzerland) 21 19832838
2005 MIB-1 and PCNA immunostaining as a diagnostic adjunct to cervical Pap smear. Diagnostic cytopathology 21 15945082
2023 Novel Association of the NOTCH Pathway Regulator MIB1 Gene With the Development of Bicuspid Aortic Valve. JAMA cardiology 20 37405741
2018 MIB1 mutations reduce Notch signaling activation and contribute to congenital heart disease. Clinical science (London, England : 1979) 20 30322850
2007 Histological grading and MIB-1 labeling index of soft-tissue sarcomas. Pathology international 20 17295643
2007 MIB1 expression in basal cell layer: a diagnostic tool to identify premalignancies of the vulva. Modern pathology : an official journal of the United States and Canadian Academy of Pathology, Inc 20 17464313
2004 P27 and mib1 expression in actinic keratosis, Bowen disease, and squamous cell carcinoma. The American Journal of dermatopathology 20 14726819
1997 Correlation of MIB-1 antigen expression with transcription factors Skn-1, Oct-1, AP-2, and HPV type in cervical intraepithelial neoplasia. The Journal of pathology 20 9422986
1998 Comparative analysis of MiB1 and p53 expression in human bladder tumors and their correlation with cancer progression. European urology 19 9555552
1997 Immunoreactivity to MIB-1 in breast cancer: methodological assessment and comparison with other proliferation indices. Cell proliferation 19 9375023
2019 MicroRNA‑198 suppresses prostate tumorigenesis by targeting MIB1. Oncology reports 18 31322262
2023 Early warning of MIB episode based on gene abundance and expression in drinking water reservoirs. Water research 17 36724724
2007 Utility of SKP2 and MIB-1 in grading follicular lymphoma using quantitative imaging analysis. Human pathology 17 17350668
1996 Significance of MIB-1, PCNA indices, and p53 protein over-expression in intramedullary tumors of the spinal cord. Noshuyo byori = Brain tumor pathology 17 8916130
2008 Expression of p16INK4a and MIB-1 in relation to histopathology and HPV types in cervical adenocarcinoma. International journal of oncology 16 18202755
2000 Cerebral granular cell astrocytomas: a Mib-1, bcl-2, and telomerase study. Clinical neuropathology 16 10919348
2023 The TDRD3-USP9X complex and MIB1 regulate TOP3B homeostasis and prevent deleterious TOP3B cleavage complexes. Nature communications 15 37980342
2004 CD44s expression, in benign, borderline and malignant tumors of ovarian surface epithelium. Correlation with p53, steroid receptor status, proliferative indices (PCNA, MIB1) and survival. Anticancer research 15 15274338
1997 MIB-1 expression in breast carcinomas with medullary features. An immunohistological study including correlations with p53 and bcl-2. Virchows Archiv : an international journal of pathology 15 9293894
2011 Frequency of Ki-67 (MIB-1) and P53 expressions among patients with prostate cancer. Indian journal of pathology & microbiology 14 22234091
2002 MIB-1 expression in cervical Papanicolaou tests correlates with dysplasia in subsequent cervical biopsies. Applied immunohistochemistry & molecular morphology : AIMM 14 11893030
1999 MIB-1 immunoreactivity correlates with blood vessel density and survival in disseminated malignant melanoma. Oncology 14 10545794
2023 Sanggenon C inhibits cell proliferation and induces apoptosis by regulating the MIB1/DAPK1 axis in glioblastoma. MedComm 13 37346933
2023 SNORA73B promotes endometrial cancer progression through targeting MIB1 and regulating host gene RCC1 alternative splicing. Journal of cellular and molecular medicine 13 37488742
2023 MIB-derived odor management based upon hydraulic regulation in small drinking water reservoirs: Principle and application. Water research 13 37611357
2016 Survivin, caspase-3 and MIB-1 expression in astrocytic tumors of various grades. Advances in medical sciences 13 26995334
2004 Orbital rhabdomyosarcoma: relationship between DNA ploidy, p53, bcl-2, MDR-1 and Ki67 (MIB1) expression and clinical behavior. Anticancer research 13 15015604
2002 Differential diagnosis of keratoacanthoma and squamous cell carcinoma of the epidermis by MIB-1 immunohistometry. Anticancer research 13 12530035
1998 MIB-1 and PC-10 immunostaining for the assessment of proliferative activity in primary acquired melanosis without and with atypia. The British journal of ophthalmology 13 9924341
2022 Population-based estimate for the correlation of the Oncotype Dx Breast Recurrence Score® result and Ki-67 IHC MIB-1 pharmDx in HR+, HER2-, node-positive early breast cancer. Breast cancer research : BCR 12 36320066
2021 FORGE: A Novel Scoring System to Predict the MIB-1 Labeling Index in Intracranial Meningiomas. Cancers 12 34298854
2021 Evaluation of the MIB-producing potential based on real-time qPCR in drinking water reservoirs. Environmental research 12 34757030
2016 Mib1 modulates dynamin 2 recruitment via Snx18 to promote Dll1 endocytosis for efficient Notch signaling. Genes to cells : devoted to molecular & cellular mechanisms 12 26923255
2012 Towards MIB-1 and p53 detection in glioma magnetic resonance image: a novel computational image analysis method. Physics in medicine and biology 12 23202049
2002 bcl-2 and MIB-1 labeling indexes in cats with lymphoma. Journal of veterinary internal medicine 12 12465771
2001 Comparison of microcirculation patterns and MIB-1 immunoreactivity in iris and posterior uveal melanoma. Ophthalmology 12 11158814
1997 Tumor cell counting using an image analysis program for MIB-1 immunohistochemistry. Neurologia medico-chirurgica 12 9059038

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