热休克因子1通过与MTA1结合来抑制雌激素依赖性转录。

Heat shock factor 1 represses estrogen-dependent transcription through association with MTA1.

作者信息

Khaleque M A, Bharti A, Gong J, Gray P J, Sachdev V, Ciocca D R, Stati A, Fanelli M, Calderwood S K

机构信息

Department of Radiation Oncology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 2215, USA.

出版信息

Oncogene. 2008 Mar 20;27(13):1886-93. doi: 10.1038/sj.onc.1210834. Epub 2007 Oct 8.

DOI:10.1038/sj.onc.1210834

PMID:17922035

Abstract

Heat shock factor 1 (HSF1), the transcriptional activator of the heat shock genes, is increasingly implicated in cancer. We have shown that HSF1 binds to the corepressor metastasis-associated protein 1 (MTA1) in vitro and in human breast carcinoma samples. HSF1-MTA1 complex formation was strongly induced by the transforming ligand heregulin and complexes incorporated a number of additional proteins including histone deacetylases (HDAC1 and 2) and Mi2alpha, all components of the NuRD corepressor complex. These complexes were induced to assemble on the chromatin of MCF7 breast carcinoma cells and associated with the promoters of estrogen-responsive genes. Such HSF1 complexes participate in repression of estrogen-dependent transcription in breast carcinoma cells treated with heregulin and this effect was inhibited by MTA1 knockdown. Repression of estrogen-dependent transcription may contribute to the role of HSF1 in cancer.

摘要

热休克因子1（HSF1）作为热休克基因的转录激活因子，与癌症的关系日益密切。我们已经证明，HSF1在体外和人类乳腺癌样本中均能与共抑制因子转移相关蛋白1（MTA1）结合。转化配体 heregulin 能强烈诱导HSF1-MTA1复合物的形成，且该复合物还包含许多其他蛋白质，包括组蛋白去乙酰化酶（HDAC1和2）以及Mi2α，它们都是核小体重塑去乙酰化酶（NuRD）共抑制复合物的组成成分。这些复合物被诱导组装在MCF7乳腺癌细胞的染色质上，并与雌激素反应基因的启动子相关联。此类HSF1复合物参与了用 heregulin处理的乳腺癌细胞中雌激素依赖性转录的抑制过程，而这种作用会被MTA1基因敲低所抑制。雌激素依赖性转录的抑制可能有助于HSF1在癌症中发挥作用。