Pognonec P, Boulukos K E, Aperlo C, Fujimoto M, Ariga H, Nomoto A, Kato H
Centre de Biochimie, Universite de Nice, France.
Oncogene. 1997 May 1;14(17):2091-8. doi: 10.1038/sj.onc.1201046.
Heterodimerization among the basic-leucine zipper (bZIP) proteins or among the basic-helix-loop-helix-leucine zipper (bHLHZip) proteins confers a multitude of combinational activities to these transcription factors. To further examine the function of the bHLHZip protein, USF, we screened for cellular proteins which could directly interact with USF using the yeast two-hybrid system. A bZip protein, Fra1, was found to efficiently interact with USF. USF specifically interacts with Fra1 but not with other closely related family members, c-Fos, Fra2, FosB, or with c-Jun. Both the bHLHZip and the N-terminal regions of Fra1 are required for efficient interaction with USF. In vivo association between USF and Fra1 has been demonstrated by co-immunoprecipitation. Expression of exogenous USF led to a decrease in AP1-dependent transcription in F9 cells. Co-expression of exogenous Fra1 restored the AP1 activity in a dose-dependent manner. These data show that USF and Fra1 physically and functionally interact demonstrating that cross-talk occurs between factors of distantly related transcription families.
碱性亮氨酸拉链（bZIP）蛋白之间或碱性螺旋-环-螺旋-亮氨酸拉链（bHLHZip）蛋白之间的异源二聚化赋予了这些转录因子多种组合活性。为了进一步研究bHLHZip蛋白USF的功能，我们使用酵母双杂交系统筛选了能够直接与USF相互作用的细胞蛋白。发现一种bZip蛋白Fra1能有效地与USF相互作用。USF特异性地与Fra1相互作用，而不与其他密切相关的家族成员c-Fos、Fra2、FosB或c-Jun相互作用。Fra1的bHLHZip和N端区域都是与USF有效相互作用所必需的。通过共免疫沉淀已证明USF与Fra1在体内存在关联。外源性USF的表达导致F9细胞中AP1依赖性转录减少。外源性Fra1的共表达以剂量依赖的方式恢复了AP1活性。这些数据表明USF和Fra1在物理和功能上相互作用，证明了远缘相关转录家族的因子之间存在相互作用。
