Qi Chao, Chang Jeffrey, Zhu Yiwei, Yeldandi Anjana V, Rao Sambasiva M, Zhu Yi-Jun
Department of Pathology, The Feinberg School of Medicine, Northwestern University, Chicago, Illinois 60611, USA.
J Biol Chem. 2002 Aug 9;277(32):28624-30. doi: 10.1074/jbc.M201053200. Epub 2002 May 30.
In an attempt to isolate cofactors capable of influencing estrogen receptor alpha (ERalpha) transcriptional activity, we used yeast two-hybrid screening and identified protein arginine methyltransferase 2 (PRMT2) as a new ERalpha-binding protein. PRMT2 interacted directly with three ERalpha regions including AF-1, DNA binding domain, and hormone binding domain in a ligand-independent fashion. The ERalpha-interacting region on PRMT2 has been mapped to a region encompassing amino acids 133-275. PRMT2 also binds to ERbeta, PR, TRbeta, RARalpha, PPARgamma, and RXRalpha in a ligand-independent manner. PRMT2 enhanced both ERalpha AF-1 and AF-2 transcriptional activity, and the potential methyltransferase activity of PRMT2 appeared pivotal for its coactivator function. In addition, PRMT2 enhanced PR, PPARgamma, and RARalpha-mediated transactivation. Although PRMT2 was found to interact with two other coactivators, the steroid receptor coactivator-1 (SRC-1) and the peroxisome proliferator-activated receptor-interacting protein (PRIP), no synergistic enhancement of ERalpha transcriptional activity was observed when PRMT2 was coexpressed with either PRIP or SRC-1. In this respect PRMT2 differs from coactivators PRMT1 and CARM1 (coactivator-associated arginine methyltransferase). These results suggest that PRMT2 is a novel ERalpha coactivator.
为了分离能够影响雌激素受体α（ERα）转录活性的辅助因子，我们采用酵母双杂交筛选方法，并鉴定出蛋白精氨酸甲基转移酶2（PRMT2）作为一种新的ERα结合蛋白。PRMT2以不依赖配体的方式直接与ERα的三个区域相互作用，包括激活功能域1（AF-1）、DNA结合结构域和激素结合结构域。PRMT2上与ERα相互作用的区域已定位到包含氨基酸133 - 275的区域。PRMT2还以不依赖配体的方式与ERβ、孕激素受体（PR）、甲状腺激素受体β（TRβ）、视黄酸受体α（RARα）、过氧化物酶体增殖物激活受体γ（PPARγ）和视黄醇X受体α（RXRα）结合。PRMT2增强了ERα的AF-1和AF-2转录活性，并且PRMT2潜在的甲基转移酶活性似乎对其共激活因子功能至关重要。此外，PRMT2增强了PR、PPARγ和RARα介导的反式激活。尽管发现PRMT2与另外两种共激活因子，即类固醇受体共激活因子-1（SRC-1）和过氧化物酶体增殖物激活受体相互作用蛋白（PRIP）相互作用，但当PRMT2与PRIP或SRC-1共表达时，未观察到ERα转录活性的协同增强。在这方面，PRMT2不同于共激活因子PRMT1和共激活因子相关精氨酸甲基转移酶1（CARM1）。这些结果表明PRMT2是一种新型的ERα共激活因子。
