The DOI matches its Crossref record; 8 of the 8 references it cites were found in a registry or an index.
Cyclin-dependent kinases regulate epigenetic gene silencing through phosphorylation of EZH2
Open accessAbstract
The Polycomb group (PcG) protein, enhancer of zeste homologue 2 (EZH2), has an essential role in promoting histone H3 lysine 27 trimethylation (H3K27me3) and epigenetic gene silencing. This function of EZH2 is important for cell proliferation and inhibition of cell differentiation, and is implicated in cancer progression. Here, we demonstrate that under physiological conditions, cyclin-dependent kinase 1 (CDK1) and cyclin-dependent kinase 2 (CDK2) phosphorylate EZH2 at Thr 350 in an evolutionarily conserved motif. Phosphorylation of Thr 350 is important for recruitment of EZH2 and maintenance of H3K27me3 levels at EZH2-target loci. Blockage of Thr 350 phosphorylation not only diminishes the global effect of EZH2 on gene silencing, it also mitigates EZH2-mediated cell proliferation and migration. These results demonstrate that CDK-mediated phosphorylation is a key mechanism governing EZH2 function and that there is a link between the cell-cycle machinery and epigenetic gene silencing.
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Cites
Cell cycle, CDKs and cancer: a changing paradigm
Malumbres, M., & Barbacid, M. (2009) · Nature Reviews Cancer · doi:10.1038/nrc2602 · Cited by 3,957 · cited 1×
“Because CDK activity is often elevated in human cancer”
BackgroundRole of Histone H3 Lysine 27 Methylation in Polycomb-Group Silencing
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Model-based analysis of oligonucleotide arrays: Expression index computation and outlier detection.
Li, C., & Wong, W. H. (2001) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.98.1.31 · Cited by 3,133
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
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EZH2 is downstream of the pRB-E2F pathway, essential for proliferation and amplified in cancer.
Bracken, A. P., Pasini, D., Capra, M., Prosperini, E., Colli, E., & Helin, K. (2003) · The EMBO Journal · doi:10.1093/emboj/cdg542 · Cited by 1,196
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Cited by
The Polycomb complex PRC2 and its mark in life
Margueron, R., & Reinberg, D. (2011) · Nature · doi:10.1038/nature09784 · Cited by 3,347
Simon, J. A., & Kingston, R. E. (2013) · Molecular Cell · doi:10.1016/j.molcel.2013.02.013 · Cited by 733
Self-citationNon-canonical functions of cell cycle cyclins and cyclin-dependent kinases
Hydbring, P., Malumbres, M., & Sicinski, P. (2016) · Nature Reviews Molecular Cell Biology · doi:10.1038/nrm.2016.27 · Cited by 528
Kaneko, S., Li, G., Son, J., Xu, C.-F., Margueron, R., Neubert, T. A., & Reinberg, D. (2010) · Genes & Development · doi:10.1101/gad.1983810 · Cited by 398
Wei, Y., Chen, Y.-H., Li, L.-Y., Lang, J., Yeh, S.-P., Shi, B., Yang, C.-C., Yang, J.-Y., Lin, C.-Y., Lai, C.-C., et al. (2011) · Nature Cell Biology · doi:10.1038/ncb2139 · Cited by 384
Metadata
- Authors
- Chen, S., Bohrer, L. R., Rai, A. N., Pan, Y., Gan, L., Zhou, X., Bagchi, A., Simon, J. A., & Huang, H.
- Venue
- Nature Cell Biology
- Published
- 2010-10-10
- Volume
- 12
- Issue
- 11
- Pages
- 1108-1114
- ISSN
- 1465-7392 (ISSN-L)
- 1476-4679
- OpenAlex
- W1987742709
- Cited by
- 281
- References
- 8
- FWCI
- 9.57
- Type
- journal article
- Language
- en
- Open access
- green
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- Chen, S., Bohrer, L. R., Rai, A. N., Pan, Y., Gan, L., Zhou, X., Bagchi, A., Simon, J. A., & Huang, H. (2010). Cyclin-dependent kinases regulate epigenetic gene silencing through phosphorylation of EZH2. Nature Cell Biology. https://doi.org/10.1038/ncb2116
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Bibliographic data: Semantic Scholar, OpenAlex, Crossref.
Contains information from the Semantic Scholar Academic Graph Datasets, made available under the ODC Attribution License (ODC-BY 1.0).
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