Hamard Pierre-Jacques, Dalbies-Tran Rozenn, Hauss Charlotte, Davidson Irwin, Kedinger Claude, Chatton Bruno
Ecole Supérieure de Biotechnologie de Strasbourg, Université Louis Pasteur, Parc d'innovation, UMR7100 CNRS-ULP, Bd. Sebastien Brant-BP10413, 67412 Strasbourg, Illkirch Cedex, France.
Oncogene. 2005 May 12;24(21):3472-83. doi: 10.1038/sj.onc.1208565.
The ATF7 proteins, which are members of the cyclic AMP responsive binding protein (CREB)/activating transcription factor (ATF) family of transcription factors, display quite versatile properties: they can interact with the adenovirus E1a oncoprotein, mediating part of its transcriptional activity; they heterodimerize with the Jun, Fos or related transcription factors, likely modulating their DNA-binding specificity; they also recruit to the promoter a stress-induced protein kinase (JNK2). In the present study, we investigate the functional relationships of ATF7 with hsTAF12 (formerly hsTAF(II)20/15), which has originally been identified as a component of the general transcription factor TFIID. We show that overexpression of hsTAF12 potentiates ATF7-induced transcriptional activation through direct interaction with ATF7, suggesting that TAF12 is a functional partner of ATF7. In support of this conclusion, chromatin immunoprecipitation experiments confirm the interaction of ATF7 with TAF12 on an ATF7-responsive promoter, in the absence of any artificial overexpression of both proteins. We also show that the TAF12-dependent transcriptional activation is competitively inhibited by TAF4. Although both TAF12 isoforms (TAF12-1 and -2, formerly TAF(II)20 and TAF(II)15) interact with the ATF7 activation region through their histone-fold domain, only the largest, hsTAF12-1, mediates transcriptional activation through its N-terminal region.
ATF7蛋白是转录因子环磷酸腺苷反应元件结合蛋白（CREB）/激活转录因子（ATF）家族的成员，具有相当多样的特性：它们可与腺病毒E1a癌蛋白相互作用，介导其部分转录活性；它们与Jun、Fos或相关转录因子形成异二聚体，可能会调节它们的DNA结合特异性；它们还会将一种应激诱导蛋白激酶（JNK2）招募至启动子。在本研究中，我们探究了ATF7与hsTAF12（以前称为hsTAF(II)20/15）之间的功能关系，hsTAF12最初被鉴定为通用转录因子TFIID的一个组分。我们发现，hsTAF12的过表达通过与ATF7直接相互作用增强了ATF7诱导的转录激活，这表明TAF12是ATF7的一个功能伙伴。为支持这一结论，染色质免疫沉淀实验证实了在两种蛋白均未人工过表达的情况下，ATF7与TAF12在一个ATF7反应性启动子上的相互作用。我们还发现，TAF4竞争性抑制了TAF12依赖的转录激活。虽然两种TAF12亚型（TAF12-1和-2，以前称为TAF(II)20和TAF(II)15）都通过其组蛋白折叠结构域与ATF7激活区域相互作用，但只有最大的hsTAF12-1通过其N端区域介导转录激活。
