The DOI matches its Crossref record; 11 of the 11 references it cites were found in a registry or an index.
Targeted disruption of the EZH2–EED complex inhibits EZH2-dependent cancer
Open accessAbstract
Enhancer of zeste homolog2 (EZH2) is the histone lysine N-methyltransferase component of the Polycomb repressive complex 2 (PRC2), which in conjunction with embryonic ectoderm development (EED) and suppressor of zeste 12 homolog (SUZ12), regulates cell lineage determination and homeostasis. Enzymatic hyperactivity has been linked to aberrant repression of tumor suppressor genes in diverse cancers. Here, we report the development of stabilized alpha-helix of EZH2 (SAH-EZH2) peptides that selectively inhibit H3 Lys27 trimethylation by dose-responsively disrupting the EZH2/EED complex and reducing EZH2 protein levels, a mechanism distinct from that reported for small molecule EZH2 inhibitors targeting the enzyme catalytic domain. MLL-AF9 leukemia cells, which are dependent on PRC2, undergo growth arrest and monocyte/macrophage differentiation upon treatment with SAH-EZH2, consistent with observed changes in expression of PRC2-regulated, lineage-specific marker genes. Thus, by dissociating the EZH2/EED complex, we pharmacologically modulate an epigenetic “writer” and suppress PRC2-dependent cancer cell growth.
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Cites
Role of Histone H3 Lysine 27 Methylation in Polycomb-Group Silencing
Cao, R., Wang, L., Wang, H., Xia, L., Erdjument-Bromage, H., Tempst, P., Jones, R. S., & Zhang, Y. (2002) · Science · doi:10.1126/science.1076997 · Cited by 3,775
The polycomb group protein EZH2 is involved in progression of prostate cancer
Varambally, S., Dhanasekaran, S. M., Zhou, M., Barrette, T. R., Kumar-Sinha, C., Sanda, M. G., Ghosh, D., Pienta, K. J., Sewalt, R. G. A. B., Otte, A. P., et al. (2002) · Nature · doi:10.1038/nature01075 · Cited by 2,717
Kleer, C. G., Cao, Q., Varambally, S., Shen, R., Ota, I., Tomlins, S. A., Ghosh, D., Sewalt, R. G. A. B., Otte, A. P., Hayes, D. F., et al. (2003) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1933744100 · Cited by 1,649
Kuzmichev, A., Nishioka, K., Erdjument-Bromage, H., Tempst, P., & Reinberg, D. (2002) · Genes & Development · doi:10.1101/gad.1035902 · Cited by 1,596
Transformation from committed progenitor to leukaemia stem cell initiated by MLL–AF9
Krivtsov, A. V., Twomey, D., Feng, Z., Stubbs, M. C., Wang, Y., Faber, J., Levine, J. E., Wang, J., Hahn, W. C., Gilliland, D. G., et al. (2006) · Nature · doi:10.1038/nature04980 · Cited by 1,513 · cited 2×
“As MLL-AF9 cells are EZH2-dependent and manifest differentiation blockade due to epigenetic deregulation 34 , we monitored the impact of SAH-EZH2-mediated disruption of PRC2 activity on the morphology of treated cells.”
Activation of Apoptosis in Vivo by a Hydrocarbon-Stapled BH3 Helix
Walensky, L. D., Kung, A. L., Escher, I., Malia, T. J., Barbuto, S., Wright, R. D., Wagner, G., Verdine, G. L., & Korsmeyer, S. J. (2004) · Science · doi:10.1126/science.1099191 · Cited by 1,349
Self-citationChromatin remodelling during development
Ho, L., & Crabtree, G. R. (2010) · Nature · doi:10.1038/nature08911 · Cited by 1,114
Tan, J., Yang, X., Zhuang, L., Jiang, X., Chen, W., Lee, P. L., Karuturi, R. K. M., Tan, P. B. O., Liu, E. T., & Yu, Q. (2007) · Genes & Development · doi:10.1101/gad.1524107 · Cited by 895 · cited 1×
“As such, EZH2 has emerged as a high priority target for therapeutic development 5–7 DZNep has been characterized as a small molecule EZH2 inhibitor that disrupts PRC2 and manifests anti-tumor activity in a variety of cancers 44–46 .”
Bracken, A. P., Kleine-Kohlbrecher, D., Dietrich, N., Pasini, D., Gargiulo, G., Beekman, C., Theilgaard-Mönch, K., Minucci, S., Porse, B. T., Marine, J.-C., et al. (2007) · Genes & Development · doi:10.1101/gad.415507 · Cited by 850
A selective inhibitor of EZH2 blocks H3K27 methylation and kills mutant lymphoma cells
Knutson, S. K., Wigle, T. J., Warholic, N. M., Sneeringer, C. J., Allain, C. J., Klaus, C. R., Sacks, J. D., Raimondi, A., Majer, C. R., Song, J., et al. (2012) · Nature Chemical Biology · doi:10.1038/nchembio.1084 · Cited by 776
Cited by
Kim, K. H., & Roberts, C. W. M. (2016) · Nature Medicine · doi:10.1038/nm.4036 · Cited by 1,471
Epigenetic balance of gene expression by Polycomb and COMPASS families
Piunti, A., & Shilatifard, A. (2016) · Science · doi:10.1126/science.aad9780 · Cited by 524
Maintaining cell identity: PRC2-mediated regulation of transcription and cancer
Comet, I., Riising, E. M., Leblanc, B., & Helin, K. (2016) · Nature Reviews Cancer · doi:10.1038/nrc.2016.83 · Cited by 432
Gan, L., Yang, Y., Li, Q., Feng, Y., Liu, T., & Guo, W. (2018) · Biomarker Research · doi:10.1186/s40364-018-0122-2 · Cited by 426
Chromatin repressive complexes in stem cells, development, and cancer
Laugesen, A., & Helin, K. (2014) · Cell stem cell · doi:10.1016/j.stem.2014.05.006 · Cited by 352
Metadata
- Authors
- Kim, W., Bird, G. H., Neff, T., Guo, G., Kerenyi, M. A., Walensky, L. D., & Orkin, S. H.
- Venue
- Nature Chemical Biology
- Published
- 2013-08-25
- Volume
- 9
- Issue
- 10
- Pages
- 643-650
- ISSN
- 1552-4450 (ISSN-L)
- 1552-4469
- OpenAlex
- W2109613178
- Cited by
- 338
- References
- 11
- FWCI
- 16.54
- Type
- journal article
- Language
- en
- Open access
- green
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