Leader Jennifer E, Wang Chenguang, Fu Maofu, Pestell Richard G
Kimmel Cancer Center, Department of Cancer Biology, Thomas Jefferson University, 233 South 10th Street, Philadelphia, PA 19107, USA.
Biochem Pharmacol. 2006 Nov 30;72(11):1589-96. doi: 10.1016/j.bcp.2006.05.024. Epub 2006 Jul 17.
Histone modifier proteins have come to the forefront in the study of gene regulation. It is now known that histone methyltransferases, acetytransferases, kinases, ubiquitinases, deacetylases and demethylases orchestrate expression of target genes by modifying both histone and non-histone proteins. The nuclear receptor (NR) superfamily govern such diverse biological processes as development, physiology and disease, including human cancer. The involvement of NR in complexes with coactivators and corepressors is necessary for regulation of target genes. This review focuses on the newly recognized interactions between the NR and histone modifying enzymes. In addition to regulating histones, the histone modifying proteins directly modify and thereby regulate NR activity. In the same manner that signaling platforms exist within the histone tails that are post-translationally processed by histone modifying proteins, cascades of post-translational modification have been identified within the NR that coordinate their activity. This review focuses on the regulation of the NR estrogen receptor (ERalpha), androgen receptor (AR) and peroxisome proliferator activated receptor-gamma (PPARgamma), given their role in tumor onset and progression.
组蛋白修饰蛋白已成为基因调控研究的前沿领域。现在已知,组蛋白甲基转移酶、乙酰转移酶、激酶、泛素酶、去乙酰化酶和去甲基酶通过修饰组蛋白和非组蛋白来协调靶基因的表达。核受体(NR)超家族调控着诸如发育、生理和疾病(包括人类癌症)等多种生物学过程。NR与共激活因子和共抑制因子形成复合物对于靶基因的调控是必需的。本综述聚焦于NR与组蛋白修饰酶之间新发现的相互作用。除了调控组蛋白外,组蛋白修饰蛋白还直接修饰并进而调控NR活性。就如同在组蛋白尾部存在由组蛋白修饰蛋白进行翻译后加工的信号平台一样,在NR内也已鉴定出协调其活性的翻译后修饰级联反应。鉴于其在肿瘤发生和进展中的作用,本综述聚焦于NR雌激素受体(ERα)、雄激素受体(AR)和过氧化物酶体增殖物激活受体γ(PPARγ)的调控。