Affinage

BMI1

Polycomb complex protein BMI-1 · UniProt P35226

Length
326 aa
Mass
36.9 kDa
Annotated
2026-06-09
100 papers in source corpus 34 papers cited in narrative 34 extracted findings
Cross-family judge vs UniProt: tie faithfulness: 7/7 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

BMI1 is a core component of Polycomb Repressive Complex 1 (PRC1) that, together with RING1A/RING1B, catalyzes mono-ubiquitination of histone H2A at K119 to enforce transcriptional repression of target loci including Hox genes and the INK4A/ARF (CDKN2A) locus, acting downstream of PRC2/EZH2-mediated H3K27 methylation (PMID:16359901, PMID:14560011). Its repressive function is exerted at numerous developmental and oncogenic loci—repressing SIK1, TGFβ2, Map3k3, Ptprm and the ERK phosphatase DUSP4 through PRC1-dependent deposition of H2AK119ub and exclusion of H3K4 trimethylation—thereby controlling stem cell maintenance, steroidogenesis, and tumor proliferation across tissues (PMID:29212025, PMID:35346195, PMID:31591477, PMID:33928089, PMID:34739857). The integrity of these activities depends on the central ubiquitin-like (UBL) domain, which mediates both homo-oligomerization and binding to the polyhomeotic protein PHC2, each required for PRC1 H2A ubiquitination and clonogenic potential (PMID:27827373). Beyond gene silencing, BMI1 is rapidly recruited to DNA double-strand breaks in an ATM/ATR-, γH2AX-, and RNF8-dependent manner, where it ubiquitinates H2A/γH2AX, promotes recruitment of 53BP1, BRCA1 and RAP80, and facilitates homologous-recombination repair by driving CtIP-dependent end resection; it also attenuates the ATM-dependent G2/M checkpoint by altering NBS1 binding to ATM (PMID:20921134, PMID:21383063, PMID:25088203, PMID:35320715). BMI1 supports stem and progenitor cell self-renewal in part by maintaining mitochondrial function and limiting reactive oxygen species, with antioxidant treatment or Chk2 deletion rescuing Bmi1-null phenotypes (PMID:19404261). BMI1 protein abundance and chromatin association are tightly controlled: 3pK/MAPKAPK3 phosphorylation dissociates PRC1 from chromatin and derepresses CDKN2A, CK2α phosphorylation at Ser110 stabilizes BMI1, and βTrCP-mediated ubiquitination targets it for proteasomal degradation (PMID:15563468, PMID:21430439, PMID:28270146). A subset of BMI1 functions are PRC1-independent, including cytoplasmic association with the SCF complex to promote IκBα ubiquitination and NF-κB signaling, and stabilization of the androgen receptor by blocking MDM2-mediated degradation (PMID:29402932, PMID:30209188).

Mechanistic history

Synthesis pass · year-by-year structured walk · 15 steps
  1. 2003 Medium

    Establishing BMI1 as a downstream effector controlling the INK4a/ARF locus connected Polycomb activity to proliferative senescence control.

    Evidence Knockout fibroblasts with retroviral Bmi1/Mel18 complementation, INK4a/ARF expression analysis

    PMID:14560011

    Open questions at the time
    • Did not define the histone modification mechanism at the locus
    • Relationship to PRC1 catalytic activity not addressed
  2. 2004 High

    Identifying 3pK/MAPKAPK3 phosphorylation of BMI1 answered how PRC1 chromatin association is dynamically reversed, linking signaling to derepression of CDKN2A.

    Evidence Yeast two-hybrid, co-IP, in vitro kinase assay, chromatin fractionation

    PMID:15563468

    Open questions at the time
    • Phosphosite(s) on BMI1 not mapped
    • In vivo physiological trigger of 3pK activation unclear
  3. 2005 High

    Demonstrating that BMI1/RING1A drives H2AK119 ubiquitination and that loss derepresses Hox genes defined BMI1's core enzymatic role within PRC1 and placed PRC2 upstream.

    Evidence Bmi1 knockout mouse, ChIP, in vitro ubiquitylation assay

    PMID:16359901

    Open questions at the time
    • Catalytic contribution of BMI1 vs RING subunit not dissected
    • Direct genome-wide target catalog not defined
  4. 2006 Medium

    Identifying E2F-1 binding to the BMI1 promoter began mapping the transcriptional inputs governing BMI1 expression.

    Evidence Luciferase reporter, ChIP, E2F-binding-site mutagenesis, inducible E2F-1-ER system

    PMID:16582100

    Open questions at the time
    • Physiological context of E2F-1 regulation of BMI1 not established
    • Other upstream factors not yet integrated
  5. 2009 High

    Linking BMI1 loss to mitochondrial dysfunction and ROS revealed a non-chromatin mechanism by which BMI1 supports cell maintenance and limits DNA damage response engagement.

    Evidence Knockout mouse, NAC pharmacological rescue, Chk2 genetic epistasis, ROS measurement

    PMID:19404261

    Open questions at the time
    • Molecular link between BMI1 and mitochondrial/redox genes unresolved
    • Whether effect is PRC1-dependent not defined
  6. 2010 High

    Recruitment of BMI1 to DSBs and ubiquitination of γH2AX established a direct role in genome stability beyond gene silencing.

    Evidence Live-cell imaging, knockdown, co-IP, ionizing radiation sensitivity assays

    PMID:20921134

    Open questions at the time
    • Precise substrate residues at break sites not fully resolved
    • Hierarchy relative to RNF8 only partly defined
  7. 2011 High

    Defining ATM/ATR- and RNF8-dependent recruitment and the requirement for BMI1 in HR repair clarified the DNA-damage signaling logic and consequences of BMI1 loss.

    Evidence Laser micro-irradiation, live imaging, siRNA, flow cytometry, co-IP

    PMID:21383063

    Open questions at the time
    • Mechanism coupling H2AK119ub to HR machinery not yet defined
    • Recruitment receptor at chromatin unclear
  8. 2011 Medium

    Identifying βTrCP-mediated degradation of BMI1 via a degron motif established post-translational control of BMI1 abundance and its oncogenic relevance.

    Evidence Reciprocal co-IP, overexpression/knockdown, site-directed mutagenesis, proteasome inhibition

    PMID:21430439

    Open questions at the time
    • Upstream signals activating βTrCP-BMI1 recognition not defined
    • Single-lab finding
  9. 2012 Medium

    UV-damage recruitment kinetics tied BMI1 chromatin engagement to acetylation status, transcription, and ATP, refining how BMI1 senses damaged chromatin.

    Evidence UV laser micro-irradiation, GFP-BMI1 FRAP/recruitment, HDAC inhibitor and ATP-depletion perturbations

    PMID:21732356

    Open questions at the time
    • Direct acetylation-sensing mechanism not identified
    • Single-lab pharmacological study
  10. 2014 Medium

    Showing BMI1 associates with NBS1 to attenuate ATM activation defined a checkpoint-modulating function distinct from repair execution.

    Evidence Co-IP, domain-deletion mutagenesis, cell-cycle flow cytometry, phospho-ATM/CHK2/p53 Western blot

    PMID:25088203

    Open questions at the time
    • Structural basis of BMI1-NBS1 interaction unknown
    • Single-lab finding
  11. 2014 Medium

    Identification of UBAP2L as a BMI1 complex partner indicated multiple distinct BMI1-containing PcG subcomplexes regulate hematopoietic stem cell activity.

    Evidence AP-MS, co-IP, shRNA knockdown, in vivo transplantation

    PMID:25185265

    Open questions at the time
    • Compositional and functional distinction of the subcomplexes incompletely defined
    • Single-lab finding
  12. 2016 High

    Structural definition of the UBL domain showed how PHC2 binding and homo-oligomerization underpin PRC1 catalytic activity and clonogenicity.

    Evidence NMR, X-ray crystallography, mutagenesis, H2A ubiquitination and clonogenic assays

    PMID:27827373

    Open questions at the time
    • Full PRC1 assembly architecture not resolved
    • How oligomerization is regulated in cells unclear
  13. 2018 Medium

    Demonstrating PRC1-independent stabilization of androgen receptor and SCF-dependent IκBα ubiquitination revealed cytoplasmic, non-chromatin BMI1 functions.

    Evidence Co-IP, protein stability assays, MDM2 manipulation, xenografts; kinase assay and Bmi1-deficient arthritis model

    PMID:29402932 PMID:30209188

    Open questions at the time
    • Structural basis of AR and SCF interactions undefined
    • Single-lab findings for each function
  14. 2022 Medium

    Showing BMI1 promotes CtIP-dependent end resection via H2AK119ub and transcriptional silencing tied its chromatin enzymatic activity directly to HR execution.

    Evidence siRNA, CtIP/RPA/RAD51 immunofluorescence, H2AK119ub ChIP, transcription-inhibitor rescue

    PMID:35320715

    Open questions at the time
    • Genome-wide scope of resection control not defined
    • Single-lab finding
  15. 2023 Medium

    A PROTAC degrader demonstrated that BMI1/RING1B stability depends on EED interaction and that selective degradation reduces H2AK119ub without affecting PRC2 activity.

    Evidence EED-linked VHL PROTAC, degradation Western blots, H2AK119ub ChIP, H3K27me3 controls

    PMID:36737841

    Open questions at the time
    • Mechanism by which EED contributes to PRC1 stability not detailed
    • Tool-compound study from single lab

Open questions

Synthesis pass · forward-looking unresolved questions
  • How BMI1's distinct PRC1-dependent and PRC1-independent activities are partitioned across tissues, and how its many transcriptional inputs and post-translational modifications are integrated to switch between repressive, DNA-repair, and cytoplasmic signaling roles, remains unresolved.
  • No unified model coordinating chromatin, DNA-repair, and cytoplasmic functions
  • Genome-wide direct target maps across cell types not consolidated
  • Regulation deciding PRC1-dependent vs independent function undefined

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0140110 transcription regulator activity 6 GO:0140096 catalytic activity, acting on a protein 5 GO:0016874 ligase activity 3 GO:0042393 histone binding 2
Localization
GO:0000228 nuclear chromosome 3 GO:0005634 nucleus 3 GO:0005829 cytosol 1
Pathway
R-HSA-4839726 Chromatin organization 4 R-HSA-74160 Gene expression (Transcription) 4 R-HSA-392499 Metabolism of proteins 3 R-HSA-73894 DNA Repair 3 R-HSA-1640170 Cell Cycle 2
Partners
ARBTRCMAPKAPK3NBS1PHC2RING1ARING1BUBAP2L
Complex memberships
PRC1

Evidence

Reading pass · 34 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2005 BMI1 and RING1A are components of the PRC1 complex that positively regulate H2A ubiquitylation at K119. Knockout of Bmi1 results in significant loss of H2A ubiquitylation and upregulation of HoxC13 expression, while EZH2-mediated H3-K27 methylation is unaffected, placing EZH2/PRC2 upstream of PRC1/BMI1 in Hox gene silencing. Knockout mouse model, chromatin immunoprecipitation (ChIP), in vitro ubiquitylation assay Molecular cell High 16359901
2009 Bmi1-deficient mouse cells display impaired mitochondrial function, marked increase in intracellular reactive oxygen species (ROS), and engagement of the DNA damage response pathway. Pharmacological antioxidant treatment (N-acetylcysteine) or genetic deletion of Chk2 improves many Bmi1-/- deficiencies, demonstrating a role for BMI1 in maintaining mitochondrial function and redox homeostasis. Knockout mouse model, pharmacological rescue with NAC, genetic epistasis (Chk2 deletion), ROS measurement Nature High 19404261
2010 BMI1 and RING2 are recruited to sites of DNA double-strand breaks (DSBs) where they contribute to ubiquitylation of γ-H2AX. Loss of BMI1 impairs recruitment of 53BP1, BRCA1, and RAP80 to DSBs, and sensitizes cells to ionizing radiation to the same extent as loss of RNF8. Simultaneous depletion of BMI1 and RNF8 shows additive radiation sensitivity. Live-cell imaging, knockdown (siRNA/shRNA), co-immunoprecipitation, ionizing radiation sensitivity assay The Journal of cell biology High 20921134
2011 BMI1 is rapidly recruited to sites of DNA damage in an ATM/ATR-dependent manner and requires H2AX phosphorylation and RNF8 recruitment. BMI1 is required for DNA damage-induced ubiquitination of histone H2A at K119. Loss of BMI1 leads to impaired repair of DSBs by homologous recombination and accumulation of cells in G2/M. Laser micro-irradiation, live-cell imaging, siRNA knockdown, flow cytometry, co-immunoprecipitation Molecular and cellular biology High 21383063
2004 MAPKAP kinase 3pK (MAPKAPK3) phosphorylates BMI1 and other PRC1 components in vivo, leading to their dissociation from chromatin. Activation or overexpression of 3pK results in dissociation of PRC complexes from chromatin and de-repression of the Cdkn2a/INK4A locus. 3pK was identified as a Bmi1 interaction partner by yeast two-hybrid and co-immunoprecipitation. Yeast two-hybrid, co-immunoprecipitation, in vitro kinase assay, chromatin fractionation, overexpression/activation studies The Journal of biological chemistry High 15563468
2011 βTrCP F-box protein recognizes a functional degron motif in BMI1, promotes its ubiquitination and proteasome-mediated degradation. Overexpression of wild-type βTrCP (but not ΔF mutant) promotes BMI1 degradation; knockdown of βTrCP increases BMI1 levels. A BMI1 mutant with altered βTrCP recognition motif is more stable and exhibits increased pro-oncogenic activity. Co-immunoprecipitation, overexpression/knockdown, site-directed mutagenesis, proteasome inhibition assays Cell cycle Medium 21430439
2016 The central ubiquitin-like (UBL) domain of BMI1 adopts a UBL fold and binds polyhomeotic protein PHC2 in a β-hairpin conformation. The UBL domain also mediates BMI1 homo-oligomerization. Both the interaction with polyhomeotic proteins and homo-oligomerization via the UBL domain are necessary for H2A ubiquitination activity of PRC1 and for clonogenic potential of U2OS cells. NMR spectroscopy, X-ray crystallography, mutagenesis, H2A ubiquitination assay, clonogenic assay Nature communications High 27827373
2010 Twist1 directly regulates BMI1 transcription, and Twist1 and BMI1 are mutually essential to promote EMT and tumour-initiating capability. Twist1 and BMI1 act cooperatively to repress expression of both E-cadherin and p16INK4a, linking EMT induction to chromatin remodeling through BMI1. Reporter assay, ChIP, siRNA knockdown, EMT/invasion assays, patient sample correlation Nature cell biology High 20818389
2018 BMI1 binds the androgen receptor (AR) protein and prevents MDM2-mediated AR protein degradation, resulting in sustained AR signaling in prostate cancer cells. This function is independent of PRC1/H2A ubiquitination activity. Co-immunoprecipitation, protein stability assay, MDM2 overexpression/knockdown, xenograft model Nature communications Medium 29402932
2014 BMI1 attenuates etoposide-induced G2/M checkpoint activation by associating with NBS1 and altering NBS1 binding to ATM, thereby reducing ATM activation (phosphorylation at S1981) and downstream phosphorylation of CHK2 (T68) and p53 (S15). BMI1 mutants lacking the PS domain or KRMK NLS fail to interact with NBS1 and lose this checkpoint-attenuating function. Co-immunoprecipitation, site-directed mutagenesis (domain deletions), flow cytometry (cell cycle), Western blot (phospho-ATM, CHK2, p53) Oncogene Medium 25088203
2022 BMI1 promotes DNA end resection during homologous recombination by facilitating recruitment of CtIP, thereby enabling RPA and RAD51 accumulation at DSB sites. H2A ubiquitylation at K119 (H2AK119ub) by BMI1 promotes end resection. Treatment with transcription inhibitors rescues end resection defects of BMI1-depleted cells, indicating that BMI1-dependent transcriptional silencing is required for end resection. siRNA knockdown, immunofluorescence (CtIP, RPA, RAD51 foci), H2AK119ub ChIP, transcription inhibitor rescue Cell reports Medium 35320715
2017 BMI1 represses the ERK inhibitor DUSP4 through a PRC1-dependent mechanism, leading to increased ERK1/2 pathway activity, and convergence with CHD7 determines chromatin accessibility at the DUSP4 locus. BMI1-mediated repression of ERK1/2 increases proliferation and tumor burden in medulloblastoma. Gene expression analysis, ChIP, ATAC-seq/chromatin accessibility, xenograft model, functional rescue Cell reports Medium 29212025
2012 BMI1 upregulates Aurora A kinase (AURKA) expression through two mechanisms: (1) activation of the Akt/β-catenin/TCF4 transcription factor complex, and (2) polycomb complex-dependent repression of miRNA let-7i, which normally suppresses AURKA. AURKA upregulation by BMI1 drives centrosomal amplification, aneuploidy, anti-apoptosis, and EMT through p53 degradation and Snail stabilization. Luciferase reporter assay, ChIP, miRNA overexpression/knockdown, in vivo tumor growth assay Cancer research Medium 23204235
2018 Bmi1 associates with the SCF ubiquitination complex via its N terminus, and following phosphorylation by IKKα/β-dependent pathway, facilitates ubiquitination of IκBα in the cytoplasm, thereby promoting NF-κB-mediated gene expression. Bmi1 deficiency inhibited NF-κB-mediated gene expression in vitro and NF-κB-mediated arthritis in vivo. Co-immunoprecipitation, kinase assay, Bmi1-deficient mouse model (arthritis model), reporter assay Journal of immunology Medium 30209188
2014 BMI1 directly binds to the promoter region of SIK1 in a complex with RING1B to promote monoubiquitination of H2A at K119 (H2AK119ub) and inhibit H3K4 trimethylation at the SIK1 locus, resulting in transcriptional repression of SIK1 and consequent promotion of osteosarcoma proliferation and metastasis. ChIP-qPCR (BMI1, RING1B, H2AK119ub, H3K4me3), knockdown/overexpression, in vitro and in vivo tumor models Cancer cell international Medium 35346195
2019 BMI1 is directly regulated by androgen receptor (AR); dihydrotestosterone (DHT) upregulates BMI1 mRNA and protein, and an AR binding site in the BMI1 promoter/enhancer region was confirmed by ChIP and gene-editing. High BMI1 expression is critical for development of castration resistance in prostate cancer. ChIP, CRISPR gene-editing, DHT stimulation, mRNA/protein quantification, xenograft model Oncogene Medium 31462713
2011 MYCN and MYC directly bind to the E-box within the BMI1 promoter (confirmed by ChIP and point-mutation assays), transactivate BMI1 gene expression, and regulate tumor proliferation through BMI1 in neuroblastoma cells. ChIP, site-directed mutagenesis (E-box point mutation), luciferase reporter, shRNA knockdown, overexpression FASEB journal Medium 21856782
2006 E2F-1 directly binds to a functional E2F binding site in the BMI1 promoter (confirmed by ChIP) and activates BMI1 transcription; deletion of the E2F binding site abolishes promoter activation by E2F-1. Luciferase reporter assay, ChIP, site-directed mutagenesis of E2F binding site, 4-OHT-regulated E2F-1-ER system Nucleic acids research Medium 16582100
2017 BMI1 upregulates ERK3 expression by suppressing miRNA let-7i (which directly targets ERK3 mRNA), thereby promoting cancer cell migration in head and neck cancer. This BMI1→let-7i→ERK3 axis was confirmed by miRNA functional assays and patient sample correlation. miRNA overexpression/knockdown, luciferase reporter (let-7i target site in ERK3 3'UTR), migration assay, patient sample analysis Molecular oncology Medium 28079973
2017 BMI1 represses expression of MDR1 in an E-box-dependent manner; ChIP shows BMI1 occupies a cluster of E-box elements on the MDR1 promoter and recruits TIP60, resulting in acetylation of histone H2A and H3 and transcriptional activation of MDR1, contributing to cisplatin resistance. ChIP, co-immunoprecipitation, gain/loss of function (siRNA and overexpression), MDR1 promoter reporter Biochimica et biophysica acta Medium 27295567
2017 BMI1 phosphorylation at Serine 110 by CK2α (a nuclear serine-threonine kinase) stabilizes BMI1 protein; prevention of phosphorylation at S110 significantly decreases BMI1 half-life and stability. Re-expression of phosphorylatable but not non-phosphorylatable BMI1 rescues clonal growth in BMI1-silenced cancer cells. Immunoprecipitation, in vitro/ex vivo kinase assay, mass spectrometry, site-directed mutagenesis, half-life assay Molecular cancer Medium 28270146
2014 UBAP2L was identified as a novel BMI1-interacting protein through isolation of BMI1-containing protein complexes and mass spectrometry. UBAP2L is part of a PcG subcomplex with BMI1. BMI1 overexpression rescues deleterious effects of UBAP2L depletion on LT-HSC activity, suggesting at least two distinct BMI1-containing PcG complexes regulate HSC activity. Affinity purification/mass spectrometry, co-immunoprecipitation, shRNA knockdown, in vivo transplantation assay Blood Medium 25185265
2019 Bmi1 drives hepatocarcinogenesis by directly binding to the TGFβ2 promoter as a co-factor of PRC1 to repress TGFβ2 expression (confirmed by ChIP and luciferase assay). Bmi1 knockdown activates TGFβ2/SMAD signaling leading to cell apoptosis via p15 and p21 upregulation; restoration of TGFβ2 blocks Bmi1/Ras-driven hepatocarcinogenesis in vivo. ChIP, luciferase reporter assay, knockout mouse model, in vivo hepatocarcinogenesis model, Western blot (SMAD pathway) Oncogene Medium 31591477
2021 BMI1 directly binds to the promoter region of Map3k3 (an upstream activator of p38 MAPK), modulates its chromatin status, and represses its expression. This repression of the p38 MAPK pathway by BMI1 promotes steroidogenesis in Leydig cells. ChIP, BMI1 knockout/knockdown, p38 MAPK pathway inhibition rescue, testosterone measurement Frontiers in cell and developmental biology Medium 33928089
2012 Acetylation status regulates BMI1 recruitment to UV-damaged chromatin. BMI1 is rapidly recruited to UV-damaged chromatin (half-time ~15 sec) simultaneously with decreased lysine acetylation. Histone hyperacetylation (via HDAC inhibitor TSA), transcription suppression, and ATP depletion all prevent BMI1 accumulation at γH2AX-positive irradiated chromatin. Live-cell confocal microscopy with UV laser micro-irradiation, GFP-BMI1 FRAP/recruitment assay, pharmacological inhibition Journal of cellular physiology Medium 21732356
2022 BMI1 promotes spermatogonial stem cell (SSC) maintenance by increasing H2AK119ub and reducing H3K4me3 at target loci. BMI1 inhibition leads to transcriptional activation of Wnt10b and nuclear translocation of β-catenin; suppression of Wnt/β-catenin signaling restores SSC maintenance in BMI1-deficient cells. ChIP (H2AK119ub, H3K4me3), BMI1 knockout/knockdown, Wnt pathway inhibition rescue, in vitro and in vivo SSC assays International journal of biological sciences Medium 35541907
2021 BMI1 promotes spermatogonia proliferation by directly binding to the Ptprm (Protein tyrosine phosphatase receptor type M) promoter, driving chromatin remodeling and gene silencing. Knockdown of Ptprm significantly improves spermatogonia proliferation in BMI1-deficient cells, establishing Ptprm as a direct transcriptional target of BMI1. ChIP, BMI1 knockout/knockdown, Ptprm siRNA rescue, in vitro and in vivo proliferation assays Biochemical and biophysical research communications Medium 34739857
2020 METTL3 mediates m6A modification in the 3' UTR of BMI1 mRNA, and promotes BMI1 translation in cooperation with m6A reader IGF2BP1, thereby driving OSCC proliferation and metastasis through increased BMI1 protein levels. MeRIP-seq, MeRIP-qPCR, luciferase reporter with mutagenesis, METTL3/IGF2BP1 knockdown/overexpression, polysome profiling Molecular therapy Medium 32621798
2016 MUC1-C drives BMI1 transcription by a MYC-dependent mechanism. MUC1-C also blocks miR-200c-mediated downregulation of BMI1. Targeting MUC1-C suppresses BMI1-induced H2A ubiquitylation and derepresses HOXC5/HOXC13. MUC1-C binds directly to BMI1 protein and promotes BMI1 occupancy on the CDKN2A promoter. Co-immunoprecipitation, ChIP, reporter assay, siRNA/shRNA knockdown, Western blot Oncogene Medium 27893710
2003 Cited2 controls expression of Bmi1 and Mel18; Cited2-/- fibroblasts have reduced Bmi1/Mel18 expression and prematurely cease proliferating due to upregulation of p16INK4a, p19ARF, and p15INK4b. Retroviral expression of Bmi1 or Mel18 in Cited2-/- fibroblasts enhances proliferation, establishing Bmi1/Mel18 as downstream effectors of Cited2 in controlling the Ink4a/ARF locus. Knockout mouse fibroblasts, retroviral complementation, Western blot, proliferation assay, Ink4a/ARF expression analysis Molecular and cellular biology Medium 14560011
2008 E2F6 cooperates with Bmi1 in the regulation of Hox gene expression and axial skeletal development in mice, but E2F6 does not cooperate with Bmi1 in repression of the Ink4a-Arf locus, indicating that the Hox and Ink4a-Arf loci are regulated by somewhat different Bmi1-containing complexes. Double-mutant mouse genetic epistasis, skeletal analysis, gene expression analysis Developmental dynamics Medium 18366140
2014 Bmi1 regulates murine intestinal stem cell proliferation downstream of Notch signaling. Loss of Bmi1 results in reduced proliferation in the ISC compartment accompanied by p16INK4a and p19ARF accumulation, and increased goblet cell differentiation resembling Notch loss-of-function. β-catenin activation partially rescues Rbpj-deletion differentiation phenotype but not ISC loss, while Bmi1 is co-regulated by both Notch and β-catenin. Tamoxifen-inducible intestine-specific conditional knockout, genetic epistasis, lineage tracing, immunostaining Development Medium 25480918
2023 A PROTAC degrader (MS147) targeting PRC1 core components BMI1 and RING1B was designed using an EED small-molecule binder linked to a VHL E3 ligase ligand. MS147 degrades BMI1/RING1B in an EED-, VHL-, ubiquitination-, and time-dependent manner, preferentially reducing H2AK119ub without affecting H3K27me3 (PRC2 activity), demonstrating that BMI1/RING1B stability depends on EED interaction. PROTAC degrader design, Western blot (protein degradation), H2AK119ub ChIP, H3K27me3 assay, siRNA controls Advanced science Medium 36737841
2019 Bmi1 suppresses adipogenesis in bone marrow stromal cells (BMSCs) by maintaining repressive epigenetic marks (H2A ubiquitylation and H3K27me3) at target loci. BMI1 represses a novel adipogenic program governed by Pax3 in BMSCs; deletion of Bmi1 from BMSCs increases marrow adipocytes, induces HSC quiescence and depletion, and impairs hematopoiesis. Conditional knockout (BMSC-specific Bmi1 deletion), ChIP (H2Aub, H3K27me3), adipogenesis assays, hematopoietic transplantation Stem cell reports Medium 31257132

Source papers

Stage 0 corpus · 100 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2005 Role of Bmi-1 and Ring1A in H2A ubiquitylation and Hox gene silencing. Molecular cell 690 16359901
2010 Bmi1 is essential in Twist1-induced epithelial-mesenchymal transition. Nature cell biology 546 20818389
2004 Bmi1 is essential for cerebellar development and is overexpressed in human medulloblastomas. Nature 435 15029199
2009 Bmi1 regulates mitochondrial function and the DNA damage response pathway. Nature 394 19404261
2004 Bmi1, stem cells, and senescence regulation. The Journal of clinical investigation 388 14722607
2012 Role of BMI1, a stem cell factor, in cancer recurrence and chemoresistance: preclinical and clinical evidences. Stem cells (Dayton, Ohio) 280 22252887
2009 BMI1 sustains human glioblastoma multiforme stem cell renewal. The Journal of neuroscience : the official journal of the Society for Neuroscience 244 19605626
2010 BMI1-mediated histone ubiquitylation promotes DNA double-strand break repair. The Journal of cell biology 235 20921134
2017 Targeting BMI1+ Cancer Stem Cells Overcomes Chemoresistance and Inhibits Metastases in Squamous Cell Carcinoma. Cell stem cell 232 28285905
2011 BMI1 is recruited to DNA breaks and contributes to DNA damage-induced H2A ubiquitination and repair. Molecular and cellular biology 220 21383063
2011 DNA methyltransferase controls stem cell aging by regulating BMI1 and EZH2 through microRNAs. PloS one 149 21572997
2008 Bmi1 is critical for lung tumorigenesis and bronchioalveolar stem cell expansion. Proceedings of the National Academy of Sciences of the United States of America 149 18697930
2004 MAPKAP kinase 3pK phosphorylates and regulates chromatin association of the polycomb group protein Bmi1. The Journal of biological chemistry 136 15563468
2020 METTL3 Promotes Tumorigenesis and Metastasis through BMI1 m6A Methylation in Oral Squamous Cell Carcinoma. Molecular therapy : the journal of the American Society of Gene Therapy 133 32621798
2016 Yin Yang 1 is associated with cancer stem cell transcription factors (SOX2, OCT4, BMI1) and clinical implication. Journal of experimental & clinical cancer research : CR 123 27225481
2006 BMI1 is a target gene of E2F-1 and is strongly expressed in primary neuroblastomas. Nucleic acids research 120 16582100
2011 BMI1 as a novel target for drug discovery in cancer. Journal of cellular biochemistry 112 21678481
2010 BMI1 and Mel-18 oppositely regulate carcinogenesis and progression of gastric cancer. Molecular cancer 97 20170541
2013 Bmi1 enhances tumorigenicity and cancer stem cell function in pancreatic adenocarcinoma. PloS one 90 23437065
2009 Bmi-1, stem cells and cancer. Acta biochimica et biophysica Sinica 86 19578716
2014 Bmi1 regulates murine intestinal stem cell proliferation and self-renewal downstream of Notch. Development (Cambridge, England) 85 25480918
2003 Transcriptional coactivator Cited2 induces Bmi1 and Mel18 and controls fibroblast proliferation via Ink4a/ARF. Molecular and cellular biology 77 14560011
2018 BMI1 regulates androgen receptor in prostate cancer independently of the polycomb repressive complex 1. Nature communications 70 29402932
2016 Inhibition of BMI1 induces autophagy-mediated necroptosis. Autophagy 67 27050456
2014 Bmi1 expression in long-term germ stem cells. Scientific reports 67 25146451
2012 Chromosome instability modulated by BMI1-AURKA signaling drives progression in head and neck cancer. Cancer research 67 23204235
2011 MYCN and MYC regulate tumor proliferation and tumorigenesis directly through BMI1 in human neuroblastomas. FASEB journal : official publication of the Federation of American Societies for Experimental Biology 66 21856782
2011 Epithelial-mesenchymal transition and cancer stemness: the Twist1-Bmi1 connection. Bioscience reports 64 21919891
2016 BMI1 regulates PRC1 architecture and activity through homo- and hetero-oligomerization. Nature communications 57 27827373
2017 BMI1 and MEL18 Promote Colitis-Associated Cancer in Mice via REG3B and STAT3. Gastroenterology 56 28780076
2008 Bmi1 is required for Hedgehog pathway-driven medulloblastoma expansion. Neoplasia (New York, N.Y.) 54 19048113
2015 Bmi1 regulates auditory hair cell survival by maintaining redox balance. Cell death & disease 53 25611380
2016 MUC1-C activates BMI1 in human cancer cells. Oncogene 52 27893710
2019 CBX4 promotes the proliferation and metastasis via regulating BMI-1 in lung cancer. Journal of cellular and molecular medicine 50 31724308
2011 βTrCP regulates BMI1 protein turnover via ubiquitination and degradation. Cell cycle (Georgetown, Tex.) 46 21430439
2012 Acetylation-dependent nuclear arrangement and recruitment of BMI1 protein to UV-damaged chromatin. Journal of cellular physiology 45 21732356
2009 Polycomb group protein Bmi1 expression in colon cancers predicts the survival. Medical oncology (Northwood, London, England) 45 19957112
2012 Bmi1 is down-regulated in the aging brain and displays antioxidant and protective activities in neurons. PloS one 44 22384090
2015 A Novel Aspect of Tumorigenesis-BMI1 Functions in Regulating DNA Damage Response. Biomolecules 43 26633535
2007 Expression of BMI-1 in normal skin and inflammatory and neoplastic skin lesions. Journal of cutaneous pathology 43 17244030
2014 MicroRNA-135a inhibits cell proliferation by targeting Bmi1 in pancreatic ductal adenocarcinoma. International journal of biological sciences 41 25013381
2020 SOX9 promotes tumor progression through the axis BMI1-p21CIP. Scientific reports 39 31941916
2019 Bmi1 Suppresses Adipogenesis in the Hematopoietic Stem Cell Niche. Stem cell reports 38 31257132
2015 BMI1 induces an invasive signature in melanoma that promotes metastasis and chemoresistance. Genes & development 38 26679841
2023 BMI1 Silencing Liposomes Suppress Postradiotherapy Cancer Stemness against Radioresistant Hepatocellular Carcinoma. ACS nano 37 37988576
2022 Hyperglycemia Enhances Immunosuppression and Aerobic Glycolysis of Pancreatic Cancer Through Upregulating Bmi1-UPF1-HK2 Pathway. Cellular and molecular gastroenterology and hepatology 36 35863742
2021 The Role of Polycomb Group Protein BMI1 in DNA Repair and Genomic Stability. International journal of molecular sciences 36 33804165
2019 Bmi1 marks gastric stem cells located in the isthmus in mice. The Journal of pathology 36 30689202
2018 The c-MYC-BMI1 axis is essential for SETDB1-mediated breast tumourigenesis. The Journal of pathology 36 29926931
2016 BMI1: A Biomarker of Hematologic Malignancies. Biomarkers in cancer 36 27168727
2018 Targeting of BMI-1 with PTC-209 inhibits glioblastoma development. Cell cycle (Georgetown, Tex.) 35 29886801
2022 BMI1 promotes osteosarcoma proliferation and metastasis by repressing the transcription of SIK1. Cancer cell international 34 35346195
2014 Polycomb group gene BMI1 controls invasion of medulloblastoma cells and inhibits BMP-regulated cell adhesion. Acta neuropathologica communications 32 24460684
2014 UBAP2L is a novel BMI1-interacting protein essential for hematopoietic stem cell activity. Blood 32 25185265
2013 Retinal degeneration depends on Bmi1 function and reactivation of cell cycle proteins. Proceedings of the National Academy of Sciences of the United States of America 32 23359713
2021 BMI1 Drives Steroidogenesis Through Epigenetically Repressing the p38 MAPK Pathway. Frontiers in cell and developmental biology 31 33928089
2012 Bmi1 is required for hepatic progenitor cell expansion and liver tumor development. PloS one 30 23029524
2022 BMI1 promotes spermatogonial stem cell maintenance by epigenetically repressing Wnt10b/β-catenin signaling. International journal of biological sciences 29 35541907
2021 LncAY controls BMI1 expression and activates BMI1/Wnt/β-catenin signaling axis in hepatocellular carcinoma. Life sciences 29 34174322
2019 LncRNA-MEG3 inhibits cell proliferation and invasion by modulating Bmi1/RNF2 in cholangiocarcinoma. Journal of cellular physiology 29 31119760
2018 Bmi1 Deficient Mice Exhibit Male Infertility. International journal of biological sciences 29 29559852
2016 Long noncoding RNA uc.338 promotes cell proliferation through association with BMI1 in hepatocellular carcinoma. Human cell 29 27154519
2022 BMI1 promotes cholangiocarcinoma progression and correlates with antitumor immunity in an exosome-dependent manner. Cellular and molecular life sciences : CMLS 28 35932322
2022 BMI-1 regulates DNA end resection and homologous recombination repair. Cell reports 27 35320715
2021 BMI1 promotes spermatogonia proliferation through epigenetic repression of Ptprm. Biochemical and biophysical research communications 27 34739857
2020 BMI1 promotes steroidogenesis through maintaining redox homeostasis in mouse MLTC-1 and primary Leydig cells. Cell cycle (Georgetown, Tex.) 27 32594840
2017 Convergence of BMI1 and CHD7 on ERK Signaling in Medulloblastoma. Cell reports 27 29212025
2014 BMI1 attenuates etoposide-induced G2/M checkpoints via reducing ATM activation. Oncogene 27 25088203
2011 BMI1 promotes the progression of laryngeal squamous cell carcinoma. Oral oncology 27 21482478
2019 BMI1 is directly regulated by androgen receptor to promote castration-resistance in prostate cancer. Oncogene 26 31462713
2018 BMI1 enhancer polymorphism underlies chromosome 10p12.31 association with childhood acute lymphoblastic leukemia. International journal of cancer 26 29923177
2017 A regulatory BMI1/let-7i/ERK3 pathway controls the motility of head and neck cancer cells. Molecular oncology 25 28079973
2016 MDR1 mediated chemoresistance: BMI1 and TIP60 in action. Biochimica et biophysica acta 25 27295567
2009 Association between Bmi1 and clinicopathological status of esophageal squamous cell carcinoma. World journal of gastroenterology 25 19452584
2019 Bmi1 drives hepatocarcinogenesis by repressing the TGFβ2/SMAD signalling axis. Oncogene 24 31591477
2018 Silencing Bmi1 expression suppresses cancer stemness and enhances chemosensitivity in endometrial cancer cells. Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie 24 30243092
2016 Potential role of Shh-Gli1-BMI1 signaling pathway nexus in glioma chemoresistance. Tumour biology : the journal of the International Society for Oncodevelopmental Biology and Medicine 24 27662839
2010 Expression and clinicopathological significance of Mel-18 and Bmi-1 mRNA in gastric carcinoma. Journal of experimental & clinical cancer research : CR 23 21059209
2008 E2f6 and Bmi1 cooperate in axial skeletal development. Developmental dynamics : an official publication of the American Association of Anatomists 23 18366140
2011 Polycomb group protein Bmi1 promotes hematopoietic cell development from embryonic stem cells. Stem cells and development 22 21545235
2023 Targeted Degradation of PRC1 Components, BMI1 and RING1B, via a Novel Protein Complex Degrader Strategy. Advanced science (Weinheim, Baden-Wurttemberg, Germany) 21 36737841
2021 BMI1 regulates multiple myeloma-associated macrophage's pro-myeloma functions. Cell death & disease 21 33993198
2020 EZH2 facilitates BMI1-dependent hepatocarcinogenesis through epigenetically silencing microRNA-200c. Oncogenesis 20 33168810
2018 Bmi1 Regulates IκBα Degradation via Association with the SCF Complex. Journal of immunology (Baltimore, Md. : 1950) 20 30209188
2017 BMI1, a new target of CK2α. Molecular cancer 20 28270146
2015 Bmi-1 Regulates Extensive Erythroid Self-Renewal. Stem cell reports 20 26028528
2012 Expression of BMI1 and p16 in laryngeal squamous cell carcinoma. Head & neck 20 22730165
2022 Roles of BMI1 in the Initiation, Progression, and Treatment of Hepatocellular Carcinoma. Technology in cancer research & treatment 19 35072573
2021 Quercetin Prevents Radiation-Induced Oral Mucositis by Upregulating BMI-1. Oxidative medicine and cellular longevity 19 34873428
2017 MicroRNA-630 inhibits breast cancer progression by directly targeting BMI1. Experimental cell research 19 29208462
2021 BMI1 in the heart: Novel functions beyond tumorigenesis. EBioMedicine 18 33421944
2018 Monoclonal Antibodies Reveal Dynamic Plasticity Between Lgr5- and Bmi1-Expressing Intestinal Cell Populations. Cellular and molecular gastroenterology and hepatology 18 29928673
2014 Expression of Bmi-1 and PAI-1 in esophageal squamous cell carcinoma. World journal of gastroenterology 18 24833884
2021 Alantolactone inhibits cervical cancer progression by downregulating BMI1. Scientific reports 17 33927214
2020 Bmi1 Maintains the Self-Renewal Property of Innate-like B Lymphocytes. Journal of immunology (Baltimore, Md. : 1950) 17 32332108
2017 BMI1 Inhibitors Down-regulate NOTCH Signaling and Suppress Proliferation of Acute Leukemia Cells. Anticancer research 17 29061784
2016 Significance of BMI1 and FSCN1 expression in colorectal cancer. Saudi journal of gastroenterology : official journal of the Saudi Gastroenterology Association 17 27488323
2015 BMI1 is expressed in canine osteosarcoma and contributes to cell growth and chemotherapy resistance. PloS one 17 26110620
2012 Linkage between Twist1 and Bmi1: molecular mechanism of cancer metastasis/stemness and clinical implications. Clinical and experimental pharmacology & physiology 17 21883379
2009 Reciprocal expression of Bmi1 and Mel-18 is associated with functioning of primitive hematopoietic cells. Experimental hematology 17 19409954

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