BMI1

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BMI1 polycomb ring finger oncogene
Protein BMI1 PDB 2ckl.png
PDB rendering based on 2ckl.
Available structures
PDB Ortholog search: PDBe, RCSB
Identifiers
Symbols BMI1 ; FLVI2/BMI1; PCGF4; RNF51
External IDs OMIM164831 MGI88174 HomoloGene121964 GeneCards: BMI1 Gene
RNA expression pattern
PBB GE BMI1 202265 at tn.png
More reference expression data
Orthologs
Species Human Mouse
Entrez 648 12151
Ensembl ENSG00000168283 ENSMUSG00000026739
UniProt P35226 P25916
RefSeq (mRNA) NM_005180 NM_007552.4
RefSeq (protein) NP_005171 NP_031578.2
Location (UCSC) Chr 10:
22.61 – 22.62 Mb
Chr 2:
18.6 – 18.61 Mb
PubMed search [1] [2]

Polycomb complex protein BMI-1 also known as polycomb group RING finger protein 4 (PCGF4) or RING finger protein 51 (RNF51) is a protein that in humans is encoded by the BMI1 gene (B cell-specific Moloney murine leukemia virus integration site 1).[1][2] BMI1 is a polycomb ring finger oncogene.

Function[edit]

BMI1 (B lymphoma Mo-MLV insertion region 1 homolog) has been reported as an oncogene by regulating p16 and p19, which are cell cycle inhibitor genes. Bmi1 knockout in mice results in defects in hematopoiesis, skeletal patterning, neurological functions, and development of the cerebellum. Recently it has been reported BMI1 is rapidly recruited to sites of DNA damage and it sustains for over than 8h. Loss of BMI1 leads to radiation sensitive and impaired repair of DNA double-strand breaks by homologous recombination 10.

Bmi1 is necessary for efficient self-renewing cell divisions of adult hematopoietic stem cells as well as adult peripheral and central nervous system neural stem cells.[3][4] However, it is less important for the generation of differentiated progeny. Given that phenotypic changes in Bmi1 knockout mice are numerous and that Bmi1 has very broad tissue distribution, it is possible that it regulates the self-renewal of other types of somatic stem cells.[5]

Bmi1 is also thought to inhibit ageing in neurons through the suppression of p53.[6]

Structure[edit]

Bmi1 has a RING finger at the N-terminus and a central helix-turn-helix domain.[7]

Clinical significance[edit]

Overexpression of Bmi1 seems to play an important role in several types of cancer, such as bladder, skin, prostate, breast, ovarian, colorectal as well as hematological malignancies. Its amplification and overexpression is especially pronounced in mantle cell lymphomas.[8] Inhibiting BMI1 has been shown to inhibit the proliferation of glioblastoma multiforme, chemoresistant ovarian cancer, prostatic, pancreatic and skin cancers.[2] Colorectal cancer stem cell self-renewal was reduced by BMI1 inhibition.[9]

Interactions[edit]

BMI1 has been shown to interact with:

References[edit]

  1. ^ Alkema MJ, Wiegant J, Raap AK, Berns A, van Lohuizen M (October 1993). "Characterization and chromosomal localization of the human proto-oncogene BMI-1". Hum. Mol. Genet. 2 (10): 1597–603. doi:10.1093/hmg/2.10.1597. PMID 8268912. 
  2. ^ a b Siddique HR, Saleem M (March 2012). "Role of BMI1, a stem cell factor, in cancer recurrence and chemoresistance: preclinical and clinical evidences". Stem Cells 30 (3): 372–8. doi:10.1002/stem.1035. PMID 22252887. 
  3. ^ Lessard J, Sauvageau G (May 2003). "Bmi-1 determines the proliferative capacity of normal and leukaemic stem cells". Nature 423 (6937): 255–60. doi:10.1038/nature01572. PMID 12714970. 
  4. ^ Molofsky AV, He S, Bydon M, Morrison SJ, Pardal R (June 2005). "Bmi-1 promotes neural stem cell self-renewal and neural development but not mouse growth and survival by repressing the p16Ink4a and p19Arf senescence pathways". Genes Dev. 19 (12): 1432–7. doi:10.1101/gad.1299505. PMC 1151659. PMID 15964994. 
  5. ^ Park IK, Morrison SJ, Clarke MF (January 2004). "Bmi1, stem cells, and senescence regulation". J. Clin. Invest. 113 (2): 175–9. doi:10.1172/JCI20800. PMC 311443. PMID 14722607. 
  6. ^ Chatoo W, Abdouh M, David J, Champagne MP, Ferreira J, Rodier F, Bernier G (January 2009). "The polycomb group gene Bmi1 regulates antioxidant defenses in neurons by repressing p53 pro-oxidant activity". J. Neurosci. 29 (2): 529–42. doi:10.1523/JNEUROSCI.5303-08.2009. PMC 2744209. PMID 19144853. 
  7. ^ Itahana K, Zou Y, Itahana Y, Martinez JL, Beausejour C, Jacobs JJ, Van Lohuizen M, Band V, Campisi J, Dimri GP (January 2003). "Control of the Replicative Life Span of Human Fibroblasts by p16 and the Polycomb Protein Bmi-1". Mol. Cell. Biol. 23 (1): 389–401. doi:10.1128/MCB.23.1.389-401.2003. PMC 140680. PMID 12482990. 
  8. ^ Shakhova O, Leung C, Marino S (August 2005). "Bmi1 in development and tumorigenesis of the central nervous system". J. Mol. Med. 83 (8): 596–600. doi:10.1007/s00109-005-0682-0. PMID 15976916. 
  9. ^ Kreso A, van Galen P, Pedley M, Lima-Fernandes E, Frelin C, Davis T, Cao L, Baiazitov R, Du W, Sydorenko N, Moon Y-C, Gibson L, Wang Y, Leung C, Iscove NN, Arrowsmith CH, Szentgyorogyi E, Gallinger S, Dick JE, O'Brien CA (January 2014). "Self-renewal as a therapeutic target in human colorectal cancer". Nat. Med. 20: 29–36. doi:10.1038/nm.3418. PMID 24292392. 
  10. ^ a b Gunster MJ, Satijn DP, Hamer KM, den Blaauwen JL, de Bruijn D, Alkema MJ, van Lohuizen M, van Driel R, Otte AP (April 1997). "Identification and characterization of interactions between the vertebrate polycomb-group protein BMI1 and human homologs of polyhomeotic". Mol. Cell. Biol. 17 (4): 2326–35. PMC 232081. PMID 9121482. 
  11. ^ a b Satijn DP, Gunster MJ, van der Vlag J, Hamer KM, Schul W, Alkema MJ, Saurin AJ, Freemont PS, van Driel R, Otte AP (July 1997). "RING1 is associated with the polycomb group protein complex and acts as a transcriptional repressor". Mol. Cell. Biol. 17 (7): 4105–13. PMC 232264. PMID 9199346. 
  12. ^ Satijn DP, Otte AP (January 1999). "RING1 interacts with multiple Polycomb-group proteins and displays tumorigenic activity". Mol. Cell. Biol. 19 (1): 57–68. PMC 83865. PMID 9858531. 
  13. ^ Barna M, Merghoub T, Costoya JA, Ruggero D, Branford M, Bergia A, Samori B, Pandolfi PP (October 2002). "Plzf mediates transcriptional repression of HoxD gene expression through chromatin remodeling". Dev. Cell 3 (4): 499–510. doi:10.1016/S1534-5807(02)00289-7. PMID 12408802. 

Further reading[edit]