Selected-GenAtlas references SOURCE GeneCards NCBI Gene Swiss-Prot Ensembl
HGNC UniGene Nucleotide OMIM UCSC
Home Page
FLASH GENE
Symbol BMI1 contributors: mct/pgu - updated : 06-11-2016
HGNC name BMI1 polycomb ring finger oncogene
HGNC id 1066
PROTEIN
PHYSICAL PROPERTIES
STRUCTURE
motifs/domains
  • N-terminal Ring-Finger (RF) domain, required for the activation of TERT transcription and immortalization of epithelial cells
  • a domain of homology to Drosophila posterior sex control (PSC)
  • two highly conserved BMI1-binding motifs, which were required for BMI1-mediated CDKN2A promoter regulation
  • a functional recognition motif for the F box protein BTRC, which regulates ubiquitination and proteasome-mediated degradation of various proteins
  • C-terminal HTHT (HT) domain, also required for the activation of TERT transcription and immortalization of epithelial cells
    • conjugated PhosphoP
    HOMOLOGY
    interspecies homolog to Drosophila Psc
    homolog to murine Bmi1 (97.5pc)
    homolog to rattus Bmi1 (95.4pc)
    intraspecies homolog to bmi-1 protooncogene
    Homologene
    FAMILY
  • polycomb gene family
    • CATEGORY transcription factor , protooncogene
    SUBCELLULAR LOCALIZATION     intracellular
    intracellular,cytoplasm
    intracellular,nucleus,nucleoplasm
    intracellular,nucleus,chromatin/chromosome
    basic FUNCTION
  • senescence regulator, involved in maintaining the transcriptionally repressive state of genes
  • playing an essential role for the generation of self-renewing adult hematopoietic stem cells and in the maintenance and expansion of immature granule cell precursors
  • involved in human colorectal carcinogenesis by repressing the INK4a/ARF proteins (CDKN2A)
  • incorporates DMAP1 in polycomb gene silencing
  • critical role for BMI1 and RING1 in H2A ubiquitylation and HOX gene silencing
  • plays a key role in regulating proliferation of both stem cells and tumor cells in diverse adult epithelial tissues
  • cooperates with FOXG1 to maintain neural stem cell self-renewal
  • is required for optimal proliferation of CD8-positive T cells
  • expression of BMI1 results in the acceleration of proliferation and colony formation in neuroblastoma cells, regulating tumorigenesis through repression of CADM1 and KIF1B
  • cooperating with MYC oncogene to produce B lymphomas
  • renders apoptotic resistance to glioma cells through NFKappaB
  • activating NFKappaB through stimulation of IKappaB phosphorylation
  • might act on cancer cells in part by blocking CDKN2A-mediated pathways
  • polycomb-group protein that maintains self-renewal
  • TWIST1 and BMI1 act cooperatively to repress expression of both E-cadherin and CDKN2A
  • TWIST1 and BMI1 are mutually essential to induce epithelial-mesenchymal transition and promote tumour-initiating capability in cancer cells
  • plays a critical role in the self-renewal of adult stem cells
  • BMI1 and RNF2 are critical components of PRC1 (Polycomb repressive complex 1) that heterodimerize via their N-terminal RING domains to form an active E3 ubiquitin ligase
  • BMI1 and PCGF2 have opposing functions and are present in distinct complexes
  • BMI1 is located downstream of ROS signaling and negatively regulated by it
  • novel regulatory pathway by which BMI1 action on GATA6 stability could alter the balance between GATA6 and NANOG protein levels to introduce a bias toward a primitive endoderm (PrE) identity in a cell-autonomous manner
  • Polycomb group protein BMI1 plays an important role in cellular homeostasis by maintaining a balance between proliferation and senescence
  • controls the cell cycle-related death process, highlighting this pathway as a promising therapeutic target for neuroprotection in retinal dystrophies
  • may reprogramme the histone acetylation profile in multiple genes through either indirect or direct binding effects which probably contributes to the malignant progression of myeloid progenitor cells
  • BMI1 expression plays a role in TERT-induced immortalisation and epithelial-mesenchymal transition (EMT)
  • regulates EMT and the migration of breast cancer cells
  • is essential for the activity of both hematopoietic stem cell and progenitor cells
  • is an essential epigenetic regulator of stem cell function during normal development and in adult organ systems
  • regulates potentially intestinal stem cell proliferation and self-renewal downstream of NOTCH1
  • KAT6A and BMI1, respectively, promoted and repressed HOX genes during the shift from the transcriptionally repressed to the active state
  • BMI1-mediated CXXC4 epigenetic suppression is crucial for enhancement of colon carcinogenesis
    • CELLULAR PROCESS nucleotide, transcription, regulation
    PHYSIOLOGICAL PROCESS
    PATHWAY
    metabolism
    signaling
    a component
  • polycomb group (PcG) component of complex with SSX1 and SSX2
  • complexing with EDR1/EDR2
  • ternary complex with DMAP1, and DNMT1
  • forms a functional complex with RNF2, but in the case of CDKN2A repression by BMI1, RNF2 was not involved and was therefore not necessary for BMI1-mediated regulation of CDKN2A
    • INTERACTION
    DNA
    RNA
    small molecule metal binding,
  • Zn2+
    • protein
  • colocolizing with RING1, HPC3
  • interacting wth DMAP1 and cooperating in gene silencing, directly interacting with DNMT-associated protein 1 (DMAP1), which has been characterized to associate with the maintenance DNA methyltransferase, DNMT1
  • link between SALL4 and BMI1 in regulating self-renewal of normal and leukemic stem cells (potential role for a SALL4/BMI1 network in leukemogenesis)
  • interacting with E4F1 (genetically interact in the hematopoietic compartment to regulate cellular proliferation)
  • direct regulation of BMI1 by TWIST1, and the functional interdependence between TWIST1 and BMI1, involved in promoting EMT and the tumour-initiating capability of head and neck cancer cells
  • wild-type BMI1 but not the mutant BMI1 interacts with BTRC
  • connection between SOX2 and BMI1 in maintaining self-renewal and identify BMI1 as a key mediator of SOX2 function
  • has a critical role in stabilizing CCNE1 by repressing the expression of FBXW7, a substrate-recognition subunit of the SCF E3 ubiquitin ligase that targets CCNE1 for degradation
  • IKZF1 is a critical BMI1 target that prevents premature lineage specification of hematopoietic stem cell (HSC)
  • BMI1 interacts with GATA6 in a Ring finger-dependent manner to confer protection against GATA6 ubiquitination and proteasomal degradation
  • CHMP1A is an essential central nervous system regulator of BMI1, which in turn is a key regulator of stem cell self-renewal
  • acts as an activator of the WNT pathway by repressing Dickkopf (DKK) family of WNT inhibitors
  • post-translational phosphorylation of NANOG is essential to regulate BMI1 and promote tumorigenesis
  • BMI1 directly bound to the promoter region of ZMYM3, which encodes a component of histone deacetylase-containing complexes
  • CDKN1A/CCNE1 pathway is crucial in modulating the anticlastogenic function of BMI1
  • UBAP2L is a novel BMI1-interacting protein, and is a novel BMI1-interacting protein essential for hematopoietic stem cell activity
  • contributes to the motility of glioma cells by regulating the expression of CDKN2A
  • SIN3B is a novel direct target of BMI1, and BMI1-driven repression of SIN3B is an essential regulator of cellular senescence
  • EPHA7 is a novel direct BMI1 target in neural cells and lymphocytes
  • BMI1 binds to the promoter of CXXC4, a Wnt antagonist, and decreases its transcription
  • ZDHHC18 and ZDHHC23 competitively interact with a BMI1 E3 ligase, RNF144A, to regulate the polyubiquitination and accumulation of BMI1
    • cell & other
    REGULATION
    induced by MYCN binding
    repressed by MEL18 )
    Other a C18Y polymorphism within the RING domain is associated with a significant decrease in BMI1 level and an elevated ubiquitination, causing its degradation
    polyubiquitinated but not leading to its proteasomal degradation
    regulation of BMI1 by the EMT regulator, TWIST1
    a positive feedback loop regulates the expression of polycomb group protein BMI1 via WNT signaling pathway
    ASSOCIATED DISORDERS
    corresponding disease(s)
    Other morbid association(s)
    TypeGene ModificationChromosome rearrangementProtein expressionProtein Function
    tumoral     --over  
    in chromic lymphocytic leukemia, mantle cell lymphoma, medulloblastoma and colorectal carcinoma
    tumoral     --other  
    differentially expressed in non small lung cancer and correlated with INK4A locus expression
    constitutional     --low  
    in primary biliary cirrhosis
    tumoral     --over  
    in non-small-cell lung cancer (NSCLC) and other epithelial malignancies, including colorectal carcinoma and liver carcinoma
    tumoral     --over  
    overexpressed in gastric cancer cell lines and tumors, correlating with advanced clinical stage and lymph node metastasis
    tumoral     --over  
    highly expressed in HCC cell lines and in particular is highly expressed in early and well differentiated HCC, correlating with ATP-binding cassette transporter B1 expression
    tumoral     --low  
    clearly reduces glioma cell migration and invasion
    tumoral   translocation    
    t(10;14)(p12;q32)/IGH-BMI1 rearrangement in chronic lymphocytic leukemia (CLL)
    tumoral       gain of function
    in colorectal cancer
    Susceptibility
    Variant & Polymorphism
    Candidate gene
    Marker
  • intestinal stem cell marker
  • marker for a subpopulation of self-renewing acinar cells in the exocrine pancreas
  • negative Bmi1 immunoexpression might serve as a marker of poor prognosis in oral tongue carcinoma patients
  • promising intracellular marker of cancer stem cells in head and neck cancer is the oncoprotein BMI1
  • BMI1&
    • 8726;CXXC4 axis is a potential novel diagnostic target of colon cancer
    Therapy target
    SystemTypeDisorderPubmed
    cancerbrain 
    attractive target for cancer therapy
    cancerbrain 
    useful indicator for glioma prognosis
    cancer  
    potent target for cancer stem cells and for the treatment of tumors
    cancerdigestivecolon
    targeting BMI1 and FSCN1 may provide potential therapeutic opportunity in colorectal cancer
    cancerdigestivecolon
    BMI1∖CXXC4 axis is a potential novel therapeutic target of colon cancer
    ANIMAL & CELL MODELS
  • activated by Moloney murine leukemia proviral insertion in Emu-myc transgenic mouse
  • mice bmi1 show protein transformation of the axial skeleton
  • mild up-regulation of Bmi1 expression in the adult stem cells of the skeletal muscle leads to a remarkable improvement of muscle function in a mouse model of Duchenne muscular dystrophy
  • in Bmi1-null mice, the cerebellar architecture was generally preserved, but the thickness of the granular and molecular layers was markedly reduced
  • transgenic mice overexpressed bmi show an anterior transformation of axial skeleton
  • mice Bmi1-/- have a shortened lifespan and develop numerous abnormalities including defects in stem cell self-renewal and thymocyte maturation. Also show a marked elevation in the intracellular levels of ROS