Zhou Qun, Shaw Patrick G, Davidson Nancy E
Department of Biochemistry and Molecular Biology, University of Maryland School of Medicine, Baltimore, Maryland 21201, USA.
Endocr Relat Cancer. 2009 Jun;16(2):319-23. doi: 10.1677/ERC-08-0305. Epub 2009 Feb 10.
The nuclear hormone receptor estrogen receptor α (ERα) promotes cellular growth through ligand-dependent activation of specific target genes, a process which is targeted in the treatment of ERα-expressing breast cancers. ERα activity is regulated at the protein level by post-translational modifications including phosphorylation and acetylation. A study now shows that ERα can also be directly methylated at lysine 302 (K302) by SET7, a histone methyltransferase that is known to monomethylate H3K4 and is associated with transcriptional activation. It was shown that K302 methylation stabilizes ERα protein and is suggested to increase sensitivity of ERα to estrogens, enhancing transcription of estrogen response elements. Furthermore, SET7 methylation of K302 is enhanced by a breast cancer-associated mutation at K303 (K303R) . These findings provide an additional mechanism of SET7 mediated transcriptional activation, as well as potential insight into the complex regulation of ERα stability and ligand sensitivity.
核激素受体雌激素受体α（ERα）通过特定靶基因的配体依赖性激活来促进细胞生长，这一过程是治疗表达ERα的乳腺癌的靶点。ERα的活性在蛋白质水平上通过包括磷酸化和乙酰化在内的翻译后修饰来调节。现在一项研究表明，ERα还可以被SET7直接甲基化在赖氨酸302（K302）位点，SET7是一种组蛋白甲基转移酶，已知可单甲基化H3K4并与转录激活相关。研究表明，K302甲基化使ERα蛋白稳定，并被认为可增加ERα对雌激素的敏感性，增强雌激素反应元件的转录。此外，K303位点的乳腺癌相关突变（K303R）会增强SET7对K302的甲基化作用。这些发现提供了SET7介导的转录激活的另一种机制，以及对ERα稳定性和配体敏感性复杂调控的潜在见解。
