EZH2

WKP

Definition: Ezh2 is a polycomb group protein. EZH2 is known to function in histone methylation, thereby regulating gene expression.

Ezh2-containing complex has been given an additional role in cellular regulation. Cytosolic Ezh2 methyltransferase complexes were shown to associate with Vav1 and control receptor-induced actin polymerization and proliferation in a methylation-dependent manner.

Overall, lysine methylation is a posttranslational modification crucial for receptor-mediated signal transduction events.

Pathology

 germline mutations

• Mutations in EZH2 cause Weaver syndrome. (22177091)

 Polycomb gene products play a crucial role in the development of highly malignant phenotypes and aggressive cancer progression in a variety of cancers.

• Overexpression of the polycomb group protein enhancer of zeste homologue 2 (EZH2) has been found in several malignancies, including prostate cancer, with an aggressive phenotype.
• Amplification of the gene has previously been demonstrated in several malignancies.
• The gene for polycomb group protein enhancer of zeste homolog 2 (EZH2) is amplified in late-stage prostate cancer (16575874).
• The amplification of the EZH2 gene is rare in early prostate cancer, whereas a fraction of late-stage tumors contains the gene amplification leading to the overexpression of the gene, thus indicating the importance of EZH2 in the progression of prostate cancer (16575874).

 salivary gland tumors

• EZH2 is a sensitive marker of malignancy in salivary gland tumors. (26377323)
• EZH2 expression in salivary gland tumors, similarly to the tumors of other organs is not characteristic for any tumor type, but is a solid marker of the malignant nature of the tumors.

 EZH2 inhibits genes responsible for suppressing tumor development, and blocking EZH2 activity may slow tumor growth.

• EZH2 has been targeted for inhibition because it is upregulated in multiple cancers including, but not limited to, breast, prostate, melanoma, and bladder cancer.

 EZH2 is involved in causing neurodegenerative symptoms in the nervous system disorder, ataxia telangiectasia.

Open references

 EZH2 is a sensitive marker of malignancy in salivary gland tumors. Hajósi-Kalcakosz S, Vincze E, Dezső K, Paku S, Rókusz A, Sápi Z, Tóth E, Nagy P. Diagn Pathol. 2015 Sep 17;10(1):163. doi : 10.1186/s13000-015-0392-z PMID: 26377323 (Free)

References

 Mutations in EZH2 Cause Weaver Syndrome. Gibson WT, Hood RL, Zhan SH, Bulman DE, Fejes AP, Moore R, Mungall AJ, Eydoux P, Babul-Hirji R, An J, Marra MA; FORGE Canada Consortium, Chitayat D, Boycott KM, Weaver DD, Jones SJ. Am J Hum Genet. 2011 Dec 14. PMID: 22177091

 Distinct expression of polycomb group proteins EZH2 and BMI1 in hepatocellular carcinoma. Yonemitsu Y, Imazeki F, Chiba T, Fukai K, Nagai Y, Miyagi S, Arai M, Aoki R, Miyazaki M, Nakatani Y, Iwama A, Yokosuka O. Hum Pathol. 2009 Apr 20. PMID: 19386347

 Saramaki OR, Tammela TL, Martikainen PM, Vessella RL, Visakorpi T. The gene for polycomb group protein enhancer of zeste homolog 2 (EZH2) is amplified in late-stage prostate cancer. Genes Chromosomes Cancer. 2006 Jul;45(7):639-45. PMID: 16575874

 The Ezh2 methyltransferase complex: actin up in the cytosol. Trends Cell Biol. 2005 Oct;15(10):514-7. PMID: 16126384