Nenasheva Valentina V, Stepanenko Ekaterina A, Makarova Irina V, Khaidarova Nella V, Antonov Stanislav A, Kozikova Larisa V, Polteva Ekaterina A, Kovaleva Galina V, Ayed Zeineb, Vovk Anastasia D, Shcherbatova Natalya A, Andreeva Lyudmila E, Tarantul Vyacheslav Z
Institute of Molecular Genetics, Russian Academy of Sciences, 2 Kurchatov Square, Moscow, Russia, 123182.
Ministry of Education and Science of Russia, D. Mendeleev University of Chemical Technology of Russia, Miusskaya Sq. 9, Moscow, Russia, 125047.
Mol Biol Rep. 2018 Dec;45(6):2087-2093. doi: 10.1007/s11033-018-4365-7. Epub 2018 Sep 10.
The tripartite-motif (TRIM)14 protein, one of the TRIM family members, was shown to participate in the antiviral and antibacterial defence. Besides, it appears to play an essential role in the processes of oncogenesis. In some types of human tumour cells, TRIM14 has been shown to inhibit apoptosis, while in others-the overexpression of TRIM14 promotes apoptosis. However, whether TRIM14 mediates apoptosis in the normal cells remains unknown. In the present study, we investigated the possible participation of the human TRIM14 gene and its mutant form (620C > T) in the induction of apoptosis in the transgenic larvae loach Misgurnus fossilis L. We observed that the expression of both forms of TRIM14 gene was accompanied by the increase of the frequency of pyknotic nuclei in fish embryos compared to control groups. Accordingly, using the TUNEL assay, the enhanced apoptosis was revealed upon expression of both forms of TRIM14 gene. The transcription of proapoptotic genes (bax, tp53, and casp9) was significantly increased in transgenic loaches expressing human wild-type TRIM14, but remained unchanged upon expression of its mutant form. In addition, the transcription of c-myc was upregulated in transgenic loaches expressing both forms. Thus, it can be assumed that during embryonic development TRIM14 has a proapoptotic effect on the cells via the activation of c-myc, tp53, and bax genes. Apparently, the mutant TRIM14 directs apoptosis via c-myc by p53-independent mechanism.
三方基序（TRIM）14蛋白是TRIM家族成员之一，已被证明参与抗病毒和抗菌防御。此外，它似乎在肿瘤发生过程中起着至关重要的作用。在某些类型的人类肿瘤细胞中，TRIM14已被证明可抑制细胞凋亡，而在其他细胞中，TRIM14的过表达则促进细胞凋亡。然而，TRIM14是否在正常细胞中介导细胞凋亡仍不清楚。在本研究中，我们调查了人类TRIM14基因及其突变形式（620C>T）在转基因幼虫泥鳅（Misgurnus fossilis L.）细胞凋亡诱导中的可能作用。我们观察到，与对照组相比，两种形式的TRIM14基因表达均伴随着鱼类胚胎中固缩核频率的增加。因此，使用TUNEL检测法，发现两种形式的TRIM14基因表达均导致细胞凋亡增强。在表达人类野生型TRIM14的转基因泥鳅中，促凋亡基因（bax、tp53和casp9）的转录显著增加，但其突变形式表达时则保持不变。此外，在表达两种形式的转基因泥鳅中，c-myc的转录上调。因此，可以推测在胚胎发育过程中，TRIM14通过激活c-myc、tp53和bax基因对细胞具有促凋亡作用。显然，突变型TRIM14通过c-myc以不依赖p53的机制指导细胞凋亡。
