EZH2

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Enhancer of zeste 2 polycomb repressive complex 2 subunit
Available structures
PDB Ortholog search: PDBe, RCSB
Identifiers
Symbols EZH2 ; ENX-1; ENX1; EZH1; EZH2b; KMT6; KMT6A; WVS; WVS2
External IDs OMIM601573 MGI107940 HomoloGene37926 GeneCards: EZH2 Gene
EC number 2.1.1.43
RNA expression pattern
PBB GE EZH2 203358 s at tn.png
More reference expression data
Orthologs
Species Human Mouse
Entrez 2146 14056
Ensembl ENSG00000106462 ENSMUSG00000029687
UniProt Q15910 Q61188
RefSeq (mRNA) NM_001203247 NM_001146689
RefSeq (protein) NP_001190176 NP_001140161
Location (UCSC) Chr 7:
148.5 – 148.58 Mb
Chr 6:
47.53 – 47.6 Mb
PubMed search [1] [2]

Histone-lysine N-methyltransferase EZH2 is an enzyme that in humans is encoded by the EZH2 gene.[1][2] Two transcript variants encoding distinct isoforms have been identified for this gene.[3]

Function[edit]

This gene encodes a member of the Polycomb-group (PcG) family. PcG family members form multimeric protein complexes, which are involved in maintaining the transcriptional repressive state of genes over successive cell generations. EZH2 acts mainly as a gene silencer; it performs this role by the addition of three methyl groups to Lysine 27 of histone 3, a modification leading to chromatin condensation.[4]

This protein associates with the embryonic ectoderm development protein, the VAV1 oncoprotein, and the X-linked nuclear protein (XNP). This protein may play a role in the hematopoietic and central nervous systems.[3]

Clinical significance[edit]

Mutations in the EZH2 gene cause Weaver syndrome.[5]

The microRNA miR-101 normally inhibits translation of the messenger RNA coding for EZH2. Loss of this microRNA gene therefore leads to increased production of EZH2.[6]

EZH2 over expression may promote cancer due to increase in histone methylation which silence the expression of tumor suppressor genes. An EZH2-targeting drug inhibits the progression of brain and prostate cancer in pre-clinical models.[7][8]

Interactions[edit]

EZH2 has been shown to interact with:


References[edit]

  1. ^ Chen H, Rossier C, Antonarakis SE (Mar 1997). "Cloning of a human homolog of the Drosophila enhancer of zeste gene (EZH2) that maps to chromosome 21q22.2". Genomics 38 (1): 30–7. doi:10.1006/geno.1996.0588. PMID 8954776. 
  2. ^ Fiskus W, Pranpat M, Balasis M, Herger B, Rao R, Chinnaiyan A, Atadja P, Bhalla K (Dec 2006). "Histone deacetylase inhibitors deplete enhancer of zeste 2 and associated polycomb repressive complex 2 proteins in human acute leukemia cells". Mol Cancer Ther 5 (12): 3096–104. doi:10.1158/1535-7163.MCT-06-0418. PMID 17172412. 
  3. ^ a b "Entrez Gene: EZH2 enhancer of zeste homolog 2 (Drosophila)". 
  4. ^ Cao R, Wang L, Wang H, Xia L, Erdjument-Bromage H, Tempst P, Jones RS, Zhang Y. (Nov 2002). "Role of histone H3 lysine 27 methylation in Polycomb-group silencing". Science 298 (5595): 1039–43. doi:10.1126/science.1076997. PMID 12351676. 
  5. ^ Gibson WT, Hood RL, Zhan SH, Bulman DE, Fejes AP, Moore R, Mungall AJ, Eydoux P, Babul-Hirji R, An J, Marra MA, Chitayat D, Boycott KM, Weaver DD, Jones SJ (December 2011). "Mutations in EZH2 Cause Weaver Syndrome". Am J Hum Genet 90 (1): 110–8. doi:10.1016/j.ajhg.2011.11.018. PMID 22177091. 
  6. ^ Smits M, Nilsson J, Mir SE, van der Stoop PM, Hulleman E, Niers JM, de Witt Hamer PC, Marquez VE, Cloos J, Krichevsky AM, Noske DP, Tannous BA, Würdinger T (December 2010). "miR-101 is down-regulated in glioblastoma resulting in EZH2-induced proliferation, migration, and angiogenesis". Oncotarget 1 (8): 710–20. PMC 3124376. PMID 21321380. 
  7. ^ Suvà ML, Riggi N, Janiszewska M, Radovanovic I, Provero P, Stehle JC, Baumer K, Le Bitoux MA, Marino D, Cironi L, Marquez VE, Clément V, Stamenkovic I (December 2009). "EZH2 is essential for glioblastoma cancer stem cell maintenance". Cancer Res. 69 (24): 9211–8. doi:10.1158/0008-5472.CAN-09-1622. PMID 19934320. 
  8. ^ Crea F, Hurt EM, Mathews LA, Cabarcas SM, Sun L, Marquez VE, Danesi R, Farrar WL (2011). "Pharmacologic disruption of Polycomb Repressive Complex 2 inhibits tumorigenicity and tumor progression in prostate cancer". Mol. Cancer 10: 40. doi:10.1186/1476-4598-10-40. PMC 3100246. PMID 21501485. 
  9. ^ Cardoso C, Timsit S, Villard L, Khrestchatisky M, Fontès M, Colleaux L (April 1998). "Specific interaction between the XNP/ATR-X gene product and the SET domain of the human EZH2 protein". Hum. Mol. Genet. 7 (4): 679–84. doi:10.1093/hmg/7.4.679. PMID 9499421. 
  10. ^ van Lohuizen M, Tijms M, Voncken JW, Schumacher A, Magnuson T, Wientjens E (June 1998). "Interaction of mouse polycomb-group (Pc-G) proteins Enx1 and Enx2 with Eed: indication for separate Pc-G complexes". Mol. Cell. Biol. 18 (6): 3572–9. PMC 108938. PMID 9584197. 
  11. ^ Denisenko O, Shnyreva M, Suzuki H, Bomsztyk K (October 1998). "Point mutations in the WD40 domain of Eed block its interaction with Ezh2". Mol. Cell. Biol. 18 (10): 5634–42. PMC 109149. PMID 9742080. 
  12. ^ a b van der Vlag J, Otte AP (December 1999). "Transcriptional repression mediated by the human polycomb-group protein EED involves histone deacetylation". Nat. Genet. 23 (4): 474–8. doi:10.1038/70602. PMID 10581039. 
  13. ^ Hobert O, Jallal B, Ullrich A (June 1996). "Interaction of Vav with ENX-1, a putative transcriptional regulator of homeobox gene expression". Mol. Cell. Biol. 16 (6): 3066–73. PMC 231301. PMID 8649418. 

Further reading[edit]