Kostrouchová Markéta, Kostrouch David, Chughtai Ahmed A, Kaššák Filip, Novotný Jan P, Kostrouchová Veronika, Benda Aleš, Krause Michael W, Saudek Vladimír, Kostrouchová Marta, Kostrouch Zdeněk
Biocev, First Faculty of Medicine, Charles University, Prague, Czech Republic.
Department of Pathology, Third Faculty of Medicine, Charles University, Prague, Czech Republic.
PeerJ. 2017 Jun 6;5:e3390. doi: 10.7717/peerj.3390. eCollection 2017.
The evolutionarily conserved Mediator complex is a critical player in regulating transcription. Comprised of approximately two dozen proteins, the Mediator integrates diverse regulatory signals through direct protein-protein interactions that, in turn, modulate the influence of Mediator on RNA Polymerase II activity. One Mediator subunit, MED28, is known to interact with cytoplasmic structural proteins, providing a potential direct link between cytoplasmic dynamics and the control of gene transcription. Although identified in many animals and plants, MED28 is not present in yeast; no bona fide MED28 has been described previously in Here, we identify bioinformatically F28F8.5, an uncharacterized predicted protein, as the nematode homologue of MED28. As in other Metazoa, F28F8.5 has dual nuclear and cytoplasmic localization and plays critical roles in the regulation of development. is a vital gene and its null mutants have severely malformed gonads and do not reproduce. F28F8.5 interacts on the protein level with the Mediator subunits MDT-6 and MDT-30. Our results indicate that F28F8.5 is an orthologue of MED28 and suggest that the potential to link cytoplasmic and nuclear events is conserved between MED28 vertebrate and nematode orthologues.
进化上保守的中介体复合物是调节转录的关键因子。中介体由大约二十多种蛋白质组成,它通过直接的蛋白质-蛋白质相互作用整合各种调节信号,进而调节中介体对RNA聚合酶II活性的影响。已知中介体亚基MED28与细胞质结构蛋白相互作用,为细胞质动态与基因转录控制之间提供了潜在的直接联系。尽管在许多动物和植物中都已鉴定出MED28,但酵母中不存在该蛋白;此前在[此处未提及具体内容]中尚未描述过真正的MED28。在这里,我们通过生物信息学方法鉴定出F28F8.5,一种未被表征的预测蛋白,作为线虫中MED28的同源物。与其他后生动物一样,F28F8.5具有细胞核和细胞质双重定位,并在发育调控中发挥关键作用。F28F8.5是一个至关重要的基因,其缺失突变体具有严重畸形的性腺且无法繁殖。F28F8.5在蛋白质水平上与中介体亚基MDT-6和MDT-30相互作用。我们的结果表明F28F8.5是MED28的直系同源物,并表明MED28脊椎动物和线虫直系同源物之间在连接细胞质和细胞核事件方面的潜力是保守的。