Affinage

MIB1

E3 ubiquitin-protein ligase MIB1 · UniProt Q86YT6

Round 2 corrected
Length
1006 aa
Mass
110.1 kDa
Annotated
2026-04-28
130 papers in source corpus 16 papers cited in narrative 16 extracted findings

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

MIB1 is a RING-domain E3 ubiquitin-protein ligase that functions as a dimer and plays a central role in Notch pathway activation by ubiquitinating the Notch ligands Delta and Jagged in signal-sending cells, thereby promoting their endocytosis and enabling productive Notch receptor engagement in neighboring cells (PMID:23314057, PMID:17331493, PMID:30322850). Beyond Notch, MIB1 ubiquitinates diverse substrates to control centriole homeostasis (Plk4), centriolar satellite integrity and ciliogenesis (PCM1, counteracted by CYLD and the SNX17–USP9X axis), directional cell migration (Ctnnd1/p120-catenin–Rac1 axis), and topoisomerase III beta proteostasis (TOP3B, counteracted by the TDRD3–USP9X complex) (PMID:25795303, PMID:31067453, PMID:29078376, PMID:37980342). Germline loss-of-function or dimerization-disrupting mutations in MIB1 cause left ventricular noncompaction cardiomyopathy and contribute to congenital heart defects including bicuspid aortic valve through impaired Notch signaling during cardiac development (PMID:23314057, PMID:37405741). In cancer contexts, MIB1-mediated degradation of ST7 and DAPK1 promotes pancreatic cancer and glioblastoma cell proliferation, respectively (PMID:33793053, PMID:37346933).

Mechanistic history

Synthesis pass · year-by-year structured walk · 9 steps
  1. 2006 High

    Establishing MIB1 as a RING-finger-dependent E3 ubiquitin ligase that ubiquitinates Delta-family Notch ligands and promotes their endocytosis resolved how ligand-presenting cells generate the mechanical or endocytic force required for Notch activation.

    Evidence In vitro and cell-based ubiquitination assays with RING domain mutants, Delta internalization assays, and genetic analysis of zebrafish mib null and antimorphic alleles

    PMID:17196985 PMID:17331493

    Open questions at the time
    • Crystal structure of MIB1 RING–substrate complex not determined
    • Precise mechanism by which ligand ubiquitination enables Notch activation (pulling force vs. recycling) unresolved
  2. 2012 High

    Conditional knockout studies in mouse demonstrated that MIB1's E3 ligase activity is required in vivo for maintaining neural progenitor pools, specifying V2 interneurons, and promoting gliogenesis—all via Notch pathway activation—extending MIB1 function beyond early embryonic patterning to tissue-specific developmental roles.

    Evidence Conditional and inducible Mib1 knockout in mouse spinal cord, chick neural tube electroporation with RING deletion mutants

    PMID:23223237

    Open questions at the time
    • Whether MIB1 substrates other than Delta/Jagged contribute to neural phenotypes is untested
    • Relative contributions of MIB1 vs. MIB2 in mammalian neurogenesis not fully delineated
  3. 2013 High

    The discovery that MIB1 dimerization is essential for function and that dimerization-disrupting mutations cause left ventricular noncompaction cardiomyopathy established MIB1 as a Mendelian disease gene and linked its Notch ligand-ubiquitinating activity to human cardiac development.

    Evidence Human autosomal-dominant pedigrees, mouse cardiac-specific Mib1 knockout, zebrafish rescue, Notch1 reporter assays

    PMID:23314057

    Open questions at the time
    • Structural basis of dimerization not resolved at atomic level
    • Whether dimerization-deficient MIB1 retains residual activity toward non-Notch substrates unknown
  4. 2015 High

    Identification of Plk4 as a MIB1 substrate at centriolar satellites, with Lys11/29/48-linked ubiquitin chains controlling Plk4 abundance, revealed a Notch-independent role for MIB1 in centriole copy-number control.

    Evidence Mass spectrometry–based ubiquitin linkage analysis, co-immunoprecipitation, E3 ligase-dead mutants, live imaging of centriole amplification

    PMID:25795303

    Open questions at the time
    • In vivo physiological consequence of MIB1-Plk4 axis (e.g., in cycling tissues) not shown
    • Whether MIB1 is the primary E3 for Plk4 or one of several is unclear
  5. 2017 High

    Demonstration that MIB1 ubiquitinates p120-catenin (Ctnnd1) at K547 to suppress Rac1 and enforce directional migration uncovered a Notch-independent cytoskeletal function, validated by rescue of zebrafish lateral line primordium migration defects.

    Evidence Site-directed mutagenesis (K547), Rac1 activity pulldown, wound-healing and zebrafish primordium live imaging, genetic epistasis

    PMID:29078376

    Open questions at the time
    • Whether Ctnnd1 ubiquitination is degradative or regulatory (signaling-type) not fully resolved
    • Upstream signals directing MIB1 toward Ctnnd1 vs. Delta/Jagged unknown
  6. 2019 High

    Two independent studies showed that MIB1 ubiquitinates PCM1 for proteasomal degradation at centriolar satellites, and that the deubiquitinases CYLD and USP9X (recruited by SNX17) counteract MIB1 to preserve PCM1 and enable ciliogenesis, establishing a ubiquitin-balance mechanism for centriolar satellite homeostasis.

    Evidence Proteomic screen for CYLD interactors, co-immunoprecipitation, ubiquitination assays, siRNA knockdown, proteasome inhibitor rescue, ciliogenesis quantification

    PMID:31067453 PMID:31671755

    Open questions at the time
    • Whether MIB1 targets other satellite proteins besides PCM1 untested
    • How serum starvation specifically activates the SNX17-USP9X protective axis mechanistically unclear
  7. 2018 Medium

    Clinical variants in MIB1 found in congenital heart disease patients were shown biochemically to reduce JAG1 ubiquitination and Notch signaling, and separately, Mib1 variants on a NOTCH1-sensitized mouse background produce bicuspid aortic valve, broadening the spectrum of MIB1-associated cardiac disease.

    Evidence Exome sequencing in CHD/BAV cohorts, ubiquitination assays with mutant MIB1, Notch reporter assays, genetically modified mice on Notch1+/− background

    PMID:30322850 PMID:37405741

    Open questions at the time
    • Penetrance and expressivity modifiers in human populations not identified
    • Whether additional MIB1 substrates contribute to valve development is unknown
  8. 2023 High

    MIB1 was found to ubiquitinate TOP3B independently of TDRD3, targeting it for proteasomal degradation; the TDRD3–USP9X complex opposes this, and failure of this balance leads to accumulation of TOP3B cleavage complexes, R-loops, and DNA damage, extending MIB1 function to genome stability.

    Evidence Co-immunoprecipitation, ubiquitination assays, siRNA depletion of MIB1/TDRD3/USP9X, TOP3Bcc and R-loop quantification, γH2AX detection

    PMID:37980342

    Open questions at the time
    • Whether MIB1-TOP3B axis operates in specific tissues or cell-cycle phases not determined
    • Direct in vivo phenotypic consequences of deregulated TOP3B turnover via MIB1 not shown
  9. 2023 Medium

    Identification of DAPK1 and ST7 as MIB1 degradation targets in glioblastoma and pancreatic cancer, respectively, implicated MIB1 E3 ligase activity in oncogenic signaling beyond Notch, though these substrates were each characterized in single-lab studies.

    Evidence Quantitative proteomics, ubiquitination assays, siRNA/overexpression rescue, xenograft tumor models

    PMID:33793053 PMID:37346933

    Open questions at the time
    • DAPK1 and ST7 as MIB1 substrates each reported by single laboratories and await independent confirmation
    • Whether MIB1 targeting of DAPK1/ST7 occurs in non-cancer contexts is unknown
    • Substrate selectivity determinants for MIB1 among its growing list of targets remain uncharacterized

Open questions

Synthesis pass · forward-looking unresolved questions
  • Key unresolved questions include the structural basis of MIB1 dimerization and substrate selectivity, how MIB1 is directed toward its diverse substrates in different cellular contexts, and whether additional disease-associated substrates exist beyond Notch ligands.
  • No high-resolution structure of full-length MIB1 or its dimer interface
  • Regulatory inputs that switch MIB1 substrate preference (Notch ligands vs. PCM1 vs. Plk4 vs. Ctnnd1 vs. TOP3B) are undefined
  • Systematic substrate profiling has not been performed

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0140096 catalytic activity, acting on a protein 12 GO:0016874 ligase activity 7
Localization
GO:0005815 microtubule organizing center 3 GO:0005886 plasma membrane 3
Pathway
R-HSA-162582 Signal Transduction 8 R-HSA-392499 Metabolism of proteins 7 R-HSA-1266738 Developmental Biology 3 R-HSA-1643685 Disease 3 R-HSA-1852241 Organelle biogenesis and maintenance 3
Partners
CTNND1CYLDDLL1JAG1PCM1PLK4TOP3BUSP9X

Evidence

Reading pass · 16 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2013 MIB1 encodes an E3 ubiquitin ligase that promotes endocytosis of NOTCH ligands DELTA and JAGGED, and functions as a dimer; germline mutations in MIB1 that disrupt dimerization cause left ventricular noncompaction cardiomyopathy (LVNC). Targeted inactivation of Mib1 in mouse myocardium abolishes ventricular Notch1 activity, causing LVNC with expansion of compact myocardium into proliferative, immature trabeculae. Human genetics (autosomal-dominant pedigrees), mouse conditional knockout, zebrafish embryo functional assays, in silico modeling, reporter assays for NOTCH1 target gene expression Nature medicine High 23314057
2007 Zebrafish Mib and Mib2 are reciprocal E3 ubiquitin ligases and substrates of each other; they function redundantly in Notch signaling using DeltaC as a common substrate. The C-terminal RING finger domain is required for E3 ubiquitin ligase activity. Mib ubiquitinates and promotes endocytosis of Delta ligands to activate Notch signaling; loss-of-function (null) mib alleles abolish Notch signaling in zebrafish embryos. Antimorphic missense (M1013R) or truncation (C785stop) mutations in the RING finger act dominant-negatively on both Mib and Mib2. In vivo zebrafish genetics (null and antimorphic alleles), co-transfection ubiquitylation assays, Delta internalization assays, domain deletion analysis Developmental biology High 17196985 17331493
2006 Zebrafish Mib and Mib2 have C-terminal RING finger-dependent E3 ubiquitin ligase activity; they are mutual substrates of each other. While both ubiquitylate DeltaC as a common substrate, Mib2 differs from Mib in its ability to promote DeltaD internalization. Mib and Mib2 bind differently to extracellular and intracellular portions of DeltaA and DeltaC. In vitro and cell-based ubiquitination assays, endocytosis/internalization assays, co-immunoprecipitation, domain mapping Journal of molecular biology High 17196985
2015 MIB1 interacts with Polo-like kinase 4 (Plk4) and localizes to centriolar satellites; upon conditions inducing centriole amplification, MIB1 redistributes to centrioles. MIB1 E3 ligase activity triggers ubiquitylation of Plk4 on multiple sites, generating Lys11-, Lys29-, and Lys48-linked ubiquitin chains, which controls Plk4 abundance and its interaction with centrosomal proteins, thereby counteracting Plk4-induced centriole amplification. Co-immunoprecipitation, mass spectrometry, in vitro and cell-based ubiquitination assays with linkage-specific analysis, MIB1 E3 ligase mutants, live imaging of centriole amplification Journal of cell science High 25795303
2012 Mib1 is an E3 ubiquitin ligase that ubiquitinates and promotes endocytosis of Notch ligands in the developing spinal cord. Conditional knockout of Mib1 in mouse spinal cord causes depletion of progenitors, premature neuronal differentiation, and imbalanced V2 interneuron specification—phenotypes identical to Notch loss of function. Late removal of Mib1 specifically suppresses gliogenesis. The RING domain of Mib1 is required for V2 interneuron specification in chick neural tube. Conditional mouse knockout, drug-inducible deletion, chick in ovo electroporation with Mib1 deletion mutants, immunofluorescence for progenitor and neuronal markers The Journal of biological chemistry High 23223237
2016 MicroRNA-10a/10b directly target the 3′-UTR of mib1 mRNA to suppress its expression. Loss of miR-10a/10b impairs blood vessel outgrowth (tip cell behavior) in zebrafish, and this phenotype is rescued by inhibition of mib1 or Notch signaling, placing Mib1 downstream of miR-10 in regulating angiogenesis in a Notch-dependent manner. In vitro luciferase reporter assay (miR-10 binding to mib1 3′-UTR), in vivo zebrafish reporter assay, morpholino knockdown of miR-10a/10b, mib1 inhibition rescue experiments Cardiovascular research Medium 26825552
2019 The tumor suppressor CYLD deubiquitinating enzyme directly deubiquitinates MIB1 to prevent MIB1 from ubiquitinating PCM1 (pericentriolar material protein 1) for proteasomal degradation. CYLD knockdown promotes PCM1 degradation, dismantles centriolar satellites, and impairs ciliogenesis; these effects are mediated through unchecked MIB1 E3 ligase activity. Proteomic screen (CYLD interactors), co-immunoprecipitation, ubiquitination assays, proteasome inhibitor rescue, siRNA knockdown, ciliogenesis assays Cell reports High 31067453
2019 SNX17 recruits the deubiquitinase USP9X to antagonize MIB1-induced ubiquitination and proteasomal degradation of PCM1 specifically during serum-starvation-induced ciliogenesis. SNX17 deficiency leads to enhanced degradation of both USP9X and PCM1 and disrupts ciliogenesis. The SNX17/USP9X axis is dispensable for PCM1 homeostasis in serum-containing media, indicating context-specific regulation of MIB1 activity. Co-immunoprecipitation, ubiquitination assays, siRNA knockdown, ciliogenesis assays, proteasome inhibitor treatment Cells Medium 31671755
2017 Mib1 ubiquitin ligase ubiquitinates Ctnnd1 (p120-catenin) at K547, which attenuates Rac1 activation in cultured cells. This Mib1-Ctnnd1-Rac1 pathway regulates persistent directional cell migration: MIB1 knockdown in HeLa cells increases random migration, and mib1 mutant zebrafish posterior lateral line primordium cells show increased random migration and loss of directional F-actin protrusions. Ctnnd1 knockdown partially rescues migration defects in mib1 mutant zebrafish. siRNA knockdown wound-closure assay, ubiquitination assays with site-specific mutagenesis (K547), Rac1 activity assay, zebrafish lateral line primordium live imaging, genetic rescue Proceedings of the National Academy of Sciences of the United States of America High 29078376
2021 MIB1 targets ST7 (suppressor of tumorigenicity 7) for ubiquitin-mediated proteasomal degradation in pancreatic cancer cells. ST7 normally suppresses tumor growth by downregulating IQGAP1; MIB1-mediated ST7 degradation relieves this suppression, thereby upregulating IQGAP1 and promoting proliferation and invasion. Co-immunoprecipitation, ubiquitination assays, proteasome inhibitor treatment, siRNA knockdown and overexpression, in vitro and xenograft in vivo proliferation/invasion assays Molecular oncology Medium 33793053
2023 MIB1 directly interacts with TOP3B (independently of TDRD3) and mediates its ubiquitylation and proteasomal degradation. The TDRD3-USP9X deubiquitinase complex acts downstream of MIB1 to stabilize TOP3B; depletion of TDRD3 increases TOP3B cleavage complexes (TOP3Bccs) in DNA and RNA, R-loops, γH2AX, and growth defects. Co-immunoprecipitation, ubiquitination assays, siRNA knockdown (USP9X, TDRD3, MIB1), TOP3Bcc measurement in DNA and RNA, R-loop detection, γH2AX immunofluorescence Nature communications High 37980342
2023 MIB1 ubiquitinates DAPK1 (death-associated protein kinase 1) to promote its proteasomal degradation in glioblastoma cells. The natural compound sanggenon C suppresses MIB1 expression, leading to DAPK1 stabilization, reduced cell proliferation, and induced apoptosis in GBM cells; MIB1 overexpression reverses these effects. Quantitative proteomics, western blotting, siRNA/overexpression, ubiquitination assays, in vitro and in vivo GBM tumor models MedComm Medium 37346933
2018 Human MIB1 pathological variants (p.T312Kfs*55 and p.W271G) identified in congenital heart disease patients significantly reduce MIB1 function, resulting in lower levels of JAGGED1 (JAG1) ubiquitination and reduced Notch signaling induction, demonstrating that MIB1-mediated ubiquitination of JAG1 is required for proper Notch pathway activation. Exome sequencing in CHD cohort, biochemical ubiquitination assays, Notch reporter assays, overexpression of mutant vs. wild-type MIB1 Clinical science Medium 30322850
2023 MIB1 variants are associated with nonsyndromic bicuspid aortic valve (nsBAV). Two mouse models carrying Mib1 variants identified in human BAV patients develop bicuspid aortic valve on a NOTCH1-sensitized background, confirming that reduced MIB1 function impairs NOTCH pathway activity during aortic valve development. Familial exome sequencing and rare variant association, genetically modified mouse models on NOTCH1-sensitized background, cardiac phenotyping JAMA cardiology Medium 37405741
2019 miR-198 directly targets MIB1 mRNA, and knockdown of MIB1 recapitulates the effects of miR-198 overexpression: reduced proliferation, G0/G1 cell cycle arrest, impaired colony formation, and reduced in vivo tumor formation in LNCaP xenografts, establishing MIB1 as a pro-tumorigenic factor in prostate cancer. Luciferase reporter assay validating miR-198 binding to MIB1 3′-UTR, siRNA knockdown of MIB1, proliferation/cell cycle/colony formation assays, LNCaP xenograft model Oncology reports Medium 31322262
2023 SNORA73B snoRNA modifies MIB1 mRNA by increasing its pseudouridine content, thereby stabilizing MIB1 mRNA and protein. Elevated MIB1 in turn increases ubiquitination of JAG1 and activates the Notch pathway to promote endometrial cancer progression. SNORA73B also regulates alternative splicing of RCC1 independent of MIB1. HPLC pseudouridine detection, actinomycin D mRNA stability assay, co-immunoprecipitation (JAG1 ubiquitination), RNA-seq, siRNA knockdown, xenograft model Journal of cellular and molecular medicine Medium 37488742

Source papers

Stage 0 corpus · 130 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2006 Global, in vivo, and site-specific phosphorylation dynamics in signaling networks. Cell 2861 17081983
2012 A promiscuous biotin ligase fusion protein identifies proximal and interacting proteins in mammalian cells. The Journal of cell biology 1850 22412018
2012 Insights into RNA biology from an atlas of mammalian mRNA-binding proteins. Cell 1718 22658674
2009 Ki67 index, HER2 status, and prognosis of patients with luminal B breast cancer. Journal of the National Cancer Institute 1642 19436038
2006 A probability-based approach for high-throughput protein phosphorylation analysis and site localization. Nature biotechnology 1336 16964243
2011 Systematic and quantitative assessment of the ubiquitin-modified proteome. Molecular cell 1334 21906983
2016 ATPase-Modulated Stress Granules Contain a Diverse Proteome and Substructure. Cell 1233 26777405
2004 Large-scale characterization of HeLa cell nuclear phosphoproteins. Proceedings of the National Academy of Sciences of the United States of America 1159 15302935
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
2014 Cell death by pyroptosis drives CD4 T-cell depletion in HIV-1 infection. Nature 909 24356306
1991 Immunobiochemical and molecular biologic characterization of the cell proliferation-associated nuclear antigen that is defined by monoclonal antibody Ki-67. The American journal of pathology 840 2012175
2018 VIRMA mediates preferential m6A mRNA methylation in 3'UTR and near stop codon and associates with alternative polyadenylation. Cell discovery 829 29507755
2005 Microarray analysis identifies a death-from-cancer signature predicting therapy failure in patients with multiple types of cancer. The Journal of clinical investigation 760 15931389
2011 A proteome-wide, quantitative survey of in vivo ubiquitylation sites reveals widespread regulatory roles. Molecular & cellular proteomics : MCP 749 21890473
2021 Dual proteome-scale networks reveal cell-specific remodeling of the human interactome. Cell 705 33961781
2012 A census of human soluble protein complexes. Cell 689 22939629
2018 Ki-67: more than a proliferation marker. Chromosoma 676 29322240
1993 The cell proliferation-associated antigen of antibody Ki-67: a very large, ubiquitous nuclear protein with numerous repeated elements, representing a new kind of cell cycle-maintaining proteins. The Journal of cell biology 670 8227122
2011 Phylogenetic-based propagation of functional annotations within the Gene Ontology consortium. Briefings in bioinformatics 656 21873635
2017 Anticancer sulfonamides target splicing by inducing RBM39 degradation via recruitment to DCAF15. Science (New York, N.Y.) 533 28302793
2022 OpenCell: Endogenous tagging for the cartography of human cellular organization. Science (New York, N.Y.) 432 35271311
2013 Ki-67 is a prognostic parameter in breast cancer patients: results of a large population-based cohort of a cancer registry. Breast cancer research and treatment 424 23674192
2010 Systematic analysis of human protein complexes identifies chromosome segregation proteins. Science (New York, N.Y.) 421 20360068
2016 Ki-67 acts as a biological surfactant to disperse mitotic chromosomes. Nature 414 27362226
2015 Panorama of ancient metazoan macromolecular complexes. Nature 407 26344197
1996 Normalization and subtraction: two approaches to facilitate gene discovery. Genome research 401 8889548
2021 A proximity-dependent biotinylation map of a human cell. Nature 339 34079125
2010 Dynamics of cullin-RING ubiquitin ligase network revealed by systematic quantitative proteomics. Cell 318 21145461
2013 Mutations in the NOTCH pathway regulator MIB1 cause left ventricular noncompaction cardiomyopathy. Nature medicine 276 23314057
2016 MIB: Metal Ion-Binding Site Prediction and Docking Server. Journal of chemical information and modeling 190 27976886
2015 Evolution and structural organization of the mitochondrial contact site (MICOS) complex and the mitochondrial intermembrane space bridging (MIB) complex. Biochimica et biophysica acta 159 26477565
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
1995 A clinicopathologic study of 233 cases with special reference to evaluation with the MIB-1 index. Cancer 100 8620403
1995 Growth activity in hyperplastic and neoplastic human thyroid determined by an immunohistochemical staining procedure using monoclonal antibody MIB-1. Human pathology 97 7860043
1998 Bcl-2 oncoprotein positivity and high MIB-1 (Ki-67) proliferative rate are independent predictive markers for recurrence in prostate carcinoma. American journal of clinical pathology 88 9763029
1999 Ki-67 labelling index and invasiveness among anterior pituitary adenomas: analysis of 103 cases using the MIB-1 monoclonal antibody. Journal of clinical pathology 84 10396237
1995 Use of the MIB-1 antibody for detecting proliferating cells in the retina. Investigative ophthalmology & visual science 80 7890504
2000 Predictive value of p53, mdm-2, p21, and mib-1 for chemotherapy response in advanced breast cancer. Clinical cancer research : an official journal of the American Association for Cancer Research 73 10955790
1998 MIB-1 labeling indices in benign, aggressive, and malignant meningiomas: a study of 90 tumors. Human pathology 73 9865827
2002 Perineural invasion and MIB-1 positivity in addition to Gleason score are significant preoperative predictors of progression after radical retropubic prostatectomy for prostate cancer. The American journal of surgical pathology 68 11914620
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
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 66 27114507
1999 Postoperative residual tumor growth of meningioma can be predicted by MIB-1 immunohistochemistry. Cancer 64 10326705
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 58 12945944
2016 MicroRNA-10a/10b represses a novel target gene mib1 to regulate angiogenesis. Cardiovascular research 57 26825552
1996 Gastric fundic gland polyps: a morphological study including mucin histochemistry, stereometry, and MIB-1 immunohistochemistry. Human pathology 57 8816883
1996 Dysembryoplastic neuroepithelial tumor: a clinicopathologic and immunohistochemical study of 11 tumors including MIB1 immunoreactivity. Clinical neuropathology 57 8998857
1999 Subependymomas: clinicopathologic study of 14 tumors, including comparative MIB-1 immunohistochemical analysis with other ependymal neoplasms. Archives of pathology & laboratory medicine 56 10320142
2000 The spectrum of neuroendocrine differentiation among gastrointestinal carcinoids: importance of histologic grading, MIB-1, p53, and bcl-2 immunoreactivity. Archives of pathology & laboratory medicine 53 10747315
2015 The E3 ubiquitin ligase Mib1 regulates Plk4 and centriole biogenesis. Journal of cell science 52 25795303
2000 Correlation between histological grade, MIB-1, p53, and recurrence in 69 completely resected primary intracranial meningiomas with a 6 year mean follow-up. Pathology, research and practice 51 10926326
2005 Immunohistochemical analysis of p53 and MIB-1 in tissue specimens obtained from endoscopic ultrasonography-guided fine needle aspiration biopsy for the diagnosis of solid pancreatic masses. Oncology reports 50 15643503
1999 Clinicopathologic study of 61 patients with ependymoma including MIB-1 immunohistochemistry. Annals of diagnostic pathology 50 9990108
1997 MIB-1 immunohistochemistry in clinical stage I nonseminomatous testicular germ cell tumors predicts patients at low risk for metastasis. Cancer 49 9128986
2007 The characterization of zebrafish antimorphic mib alleles reveals that Mib and Mind bomb-2 (Mib2) function redundantly. Developmental biology 45 17331493
1995 Meningioangiomatosis. A clinicopathologic study including MIB1 immunoreactivity. Archives of pathology & laboratory medicine 45 7487408
2002 Value of tissue markers p27(kip1), MIB-1, and CD44s for the pre-operative prediction of tumour features in screen-detected prostate cancer. The Journal of pathology 44 12015737
1997 Proliferative potential in pituitary adenomas: measurement by monoclonal antibody MIB-1. Acta neurochirurgica 43 9265953
1996 The semidominant Mi(b) mutation identifies a role for the HLH domain in DNA binding in addition to its role in protein dimerization. The EMBO journal 41 8947051
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 40 23223237
1998 Telomerase expression shows differences across multiple regions of oligodendroglioma versus high grade astrocytomas but shows correlation with Mib-1 labelling. Journal of clinical pathology 38 9659240
2016 Removal of 2-MIB and geosmin by electrogenerated persulfate: Performance, mechanism and pathways. Chemosphere 36 27914726
2006 Zebrafish Mib and Mib2 are mutual E3 ubiquitin ligases with common and specific delta substrates. Journal of molecular biology 34 17196985
2000 p53 accumulation associated with bcl-2, the proliferation marker MIB-1 and survival in patients with prostate cancer subjected to watchful waiting. The Journal of urology 34 10953132
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
1995 Hyalinizing trabecular adenoma of the thyroid: its unusual cytoplasmic immunopositivity for MIB1. Pathology international 34 7647938
1998 Phyllodes tumour of the breast: immunohistochemical study of 37 tumours using MIB1 antibody. Pathology, research and practice 33 9584322
1997 Myxopapillary ependymomas: a clinicopathologic study of 14 cases including MIB-1 and p53 immunoreactivity. Modern pathology : an official journal of the United States and Canadian Academy of Pathology, Inc 31 9110291
2017 Parafibromin, APC, and MIB-1 Are Useful Markers for Distinguishing Parathyroid Carcinomas From Adenomas. Applied immunohistochemistry & molecular morphology : AIMM 30 27490759
2000 Endocervical intraepithelial glandular atypia (dysplasia): a histopathologic, human papillomavirus, and MIB-1 analysis of 25 cases. Human pathology 29 10872657
2019 CYLD Regulates Centriolar Satellites Proteostasis by Counteracting the E3 Ligase MIB1. Cell reports 28 31067453
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
1995 Analysis of crypt cell proliferation in coeliac disease using MI-B1 antibody shows an increase in growth fraction. Gut 28 7890231
1980 Peptidase-3 (Pep-3), dipeptidase variant in the rat homologous to mouse pep-3 (Dip-1) and human PEP-c. Biochemical genetics 28 7225079
2005 Correlation between choline and MIB-1 index in human gliomas. A quantitative in proton MR spectroscopy study. Journal of clinical neuroscience : official journal of the Neurosurgical Society of Australasia 27 15925772
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
2000 Intracranial meningeal tumours in childhood: a clinicopathologic study including MIB-1 immunohistochemistry. Pathology, research and practice 26 10729919
1996 Proliferation index determined by MIB-1 and recurrence in endometrial cancer. Gynecologic oncology 26 8641618
1998 Ki-67 (MIB 5) immunostaining of mouse lung tumors induced by 4-nitroquinoline 1-oxide. Histochemistry and cell biology 25 9860257
2021 MIB1 upregulates IQGAP1 and promotes pancreatic cancer progression by inducing ST7 degradation. Molecular oncology 24 33793053
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
2001 Immunohistochemical analysis of MIB-1 proliferative activity in human endometrial cancer. Correlation with clinicopathological parameters, patient outcome, retinoblastoma immunoreactivity and K-ras codon 12 point mutations. The Histochemical journal 23 11550800
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
1998 Cyclin D1 and MIB-1 immunohistochemistry in pilocytic astrocytomas: a study of 48 cases. Human pathology 22 9865840
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
2009 Impact of morphology, MIB-1, p53 and MGMT on outcome in pilocytic astrocytomas. Brain pathology (Zurich, Switzerland) 21 19832838
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 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
2007 Epidermal growth factor receptor is involved in the development of an invasive phenotype in vulvar squamous lesions, but is not related to MIB-1 immunoreactivity. International journal of gynecological pathology : official journal of the International Society of Gynecological Pathologists 20 17885502
1998 The rat microphthalmia-associated transcription factor gene (Mitf) maps at 4q34-q41 and is mutated in the mib rats. Mammalian genome : official journal of the International Mammalian Genome Society 20 9680380
2007 Histological grading and MIB-1 labeling index of soft-tissue sarcomas. Pathology international 19 17295643
2004 P27 and mib1 expression in actinic keratosis, Bowen disease, and squamous cell carcinoma. The American Journal of dermatopathology 19 14726819
1997 Immunoreactivity to MIB-1 in breast cancer: methodological assessment and comparison with other proliferation indices. Cell proliferation 19 9375023
1994 Neonatal reductions in osteoclast number and function account for the transient nature of osteopetrosis in the rat mutation microphthalmia blanc (mib). Bone 19 7873301
2019 MicroRNA‑198 suppresses prostate tumorigenesis by targeting MIB1. Oncology reports 18 31322262
2021 PERM1 interacts with the MICOS-MIB complex to connect the mitochondria and sarcolemma via ankyrin B. Nature communications 17 34385433
2007 Utility of SKP2 and MIB-1 in grading follicular lymphoma using quantitative imaging analysis. Human pathology 17 17350668
1998 Histone mRNA in-situ hybridization in astrocytomas: a comparison with PCNA, MIB-1 and mitoses in paraffin-embedded material. Histopathology 16 9522215
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 The TDRD3-USP9X complex and MIB1 regulate TOP3B homeostasis and prevent deleterious TOP3B cleavage complexes. Nature communications 13 37980342
2021 Ecological niche and in-situ control of MIB producers in source water. Journal of environmental sciences (China) 13 34593182
2017 Re-evaluation of MIB-1 immunostaining for diagnosing hyalinizing trabecular tumour of the thyroid: semi-automated techniques with manual antigen retrieval are more accurate than fully automated techniques. Endocrine journal 13 29199205
2016 Survivin, caspase-3 and MIB-1 expression in astrocytic tumors of various grades. Advances in medical sciences 13 26995334
2011 Frequency of Ki-67 (MIB-1) and P53 expressions among patients with prostate cancer. Indian journal of pathology & microbiology 13 22234091
2023 SNORA73B promotes endometrial cancer progression through targeting MIB1 and regulating host gene RCC1 alternative splicing. Journal of cellular and molecular medicine 12 37488742
2023 MIB-derived odor management based upon hydraulic regulation in small drinking water reservoirs: Principle and application. Water research 12 37611357
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
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
1997 Tumor cell counting using an image analysis program for MIB-1 immunohistochemistry. Neurologia medico-chirurgica 12 9059038
1994 PAPNET for analysis of proliferating (MIB-1 positive) cell populations in cervical smears. European journal of morphology 12 8086271
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 11 36320066
2012 Usefulness of Ki-67 (MIB-1) immunostaining in the diagnosis of pulmonary sclerosing hemangiomas. APMIS : acta pathologica, microbiologica, et immunologica Scandinavica 11 23030396
2010 Reinke's edema: investigations on the role of MIB-1 and hepatocyte growth factor. European journal of histochemistry : EJH 11 20819770
2003 Image analysis system for assessment of immunohistochemically stained proliferative marker (MIB-1) in oesophageal squamous cell carcinoma. Computer methods and programs in biomedicine 11 12468125
2003 Interobserver variability in determining MIB-1 labeling indices in oligodendrogliomas. Annals of diagnostic pathology 11 12616468
2003 Proliferative, infiltrative, and metastatic activities in colorectal tumors assessed by MIB-1 antibody. Oncology reports 11 14534689