Macho Betina, Brancorsini Stefano, Fimia Gian Maria, Setou Mitsutoshi, Hirokawa Nobutaka, Sassone-Corsi Paolo
Institut de Génétique et de Biologie Moléculaire et Cellulaire, B. P. 10142, 67404 Illkirch, Strasbourg, France.
Science. 2002 Dec 20;298(5602):2388-90. doi: 10.1126/science.1077265.
ACT is a LIM-only protein expressed exclusively in round spermatids, where it cooperates with transcriptional activator CREM in regulating various postmeiotic genes. Targeted inactivation of CREM leads to a complete block of mouse spermiogenesis. We sought to identify the regulatory steps controlling the functional interplay between CREM and ACT. We found that ACT selectively associates with KIF17b, a kinesin highly expressed in male germ cells. The ACT-KIF17b interaction is restricted to specific stages of spermatogenesis and directly determines the intracellular localization of ACT. Sensitivity to leptomycin B indicates that KIF17b can be actively exported from the nucleus through the Crm1 receptor. Thus, a kinesin directly controls the activity of a transcriptional coactivator by a tight regulation of its intracellular localization.
ACT是一种仅含LIM结构域的蛋白质,仅在圆形精子细胞中表达,在那里它与转录激活因子CREM协同调节各种减数分裂后基因。CREM的靶向失活导致小鼠精子发生完全受阻。我们试图确定控制CREM和ACT之间功能相互作用的调控步骤。我们发现ACT选择性地与KIF17b结合,KIF17b是一种在雄性生殖细胞中高度表达的驱动蛋白。ACT与KIF17b的相互作用仅限于精子发生的特定阶段,并直接决定ACT在细胞内的定位。对雷帕霉素B的敏感性表明KIF17b可以通过Crm1受体从细胞核中主动输出。因此,一种驱动蛋白通过严格调节其细胞内定位直接控制转录共激活因子的活性。