Expression of the human TRIM14 and its mutant form (P207L) promotes apoptosis in transgenic loaches
Autor: | Irina Makarova, Ekaterina A Polteva, V V Nenasheva, Vyacheslav Z. Tarantul, Larisa V Kozikova, S A Antonov, Ekaterina A Stepanenko, Natalya Shcherbatova, Lyudmila Andreeva, Anastasia D Vovk, Zeineb Ayed, N. V. Khaidarova, G. V. Kovaleva |
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Rok vydání: | 2018 |
Předmět: |
0301 basic medicine
Transgene Mutant Apoptosis Biology medicine.disease_cause Polymorphism Single Nucleotide Animals Genetically Modified Tripartite Motif Proteins 03 medical and health sciences Transcription (biology) Cell Line Tumor Genetics medicine Animals Humans Molecular Biology Gene bcl-2-Associated X Protein TUNEL assay Intracellular Signaling Peptides and Proteins General Medicine Caspase 9 Cell biology Cypriniformes Cell Transformation Neoplastic 030104 developmental biology Tumor Suppressor Protein p53 Carrier Proteins Carcinogenesis Pyknosis Signal Transduction |
Zdroj: | Molecular Biology Reports. 45:2087-2093 |
ISSN: | 1573-4978 0301-4851 |
DOI: | 10.1007/s11033-018-4365-7 |
Popis: | 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. |
Databáze: | OpenAIRE |
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