Nakamura Hitomi, Murakami Tatsuo, Hattori Shosaku, Sakaki Yoshiyuki, Ohkuri Takatoshi, Chijiwa Takahito, Ohno Motonori, Oda-Ueda Naoko
Department of Pharmaceutical Sciences, Faculty of Pharmaceutical Sciences, Sojo University, 4-22-1 Ikeda, Nishi-ku, Kumamoto 860-0082, Japan.
Department of Applied Life Science, Faculty of Bioscience and Biotechnology, Sojo University, 4-22-1 Ikeda, Nishi-ku, Kumamoto 860-0082, Japan.
Toxicon. 2014 Dec 15;92:133-9. doi: 10.1016/j.toxicon.2014.10.001. Epub 2014 Oct 22.
Protobothrops flavoviridis (habu) (Crotalinae, Viperidae) is a Japanese venomous snake, and its venom contains the enzymes with a variety of physiological activities. The phospholipases A2 (PLA2s) are the major components and exert various toxic effects. They are expressed abundantly in the venom gland. It is thought that the venom gland-specific transcription factors play a key role for activation of PLA2 genes specifically expressed in the venom gland. Thus, the full-length cDNA library for P. flavoviridis venom gland after milking of the venom was made to explore the transcription factors therein. As a result, three cDNAs encoding epithelium-specific ETS transcription factors (ESE)-1, -2, and -3 were obtained. Among them, ESE-3 was specifically expressed in the venom gland and activated the proximal promoters of venom PLA2 genes, which are possibly regarded as the representatives of the venom gland-specific protein genes in P. flavoviridis. Interestingly, the binding specificity of ESE-3 to the ETS binding motif located near TATA box is well correlated with transcriptional activities for the venom PLA2 genes. This is the first report that venom gland-specific transcription factor could actually activate the promoters of the venom protein genes.
日本蝮蛇（日本蝮，蝰蛇科，蝮亚科）是一种日本毒蛇，其毒液含有多种具有生理活性的酶。磷脂酶A2（PLA2s）是主要成分，并发挥多种毒性作用。它们在毒腺中大量表达。据认为，毒腺特异性转录因子对激活在毒腺中特异性表达的PLA2基因起关键作用。因此，为了探索其中的转录因子，制备了采毒后的日本蝮蛇毒腺全长cDNA文库。结果，获得了三个编码上皮细胞特异性ETS转录因子（ESE）-1、-2和-3的cDNA。其中，ESE-3在毒腺中特异性表达，并激活了毒液PLA2基因的近端启动子，这些启动子可能被视为日本蝮蛇毒腺特异性蛋白基因的代表。有趣的是，ESE-3与位于TATA框附近的ETS结合基序的结合特异性与毒液PLA2基因的转录活性密切相关。这是关于毒腺特异性转录因子实际上可以激活毒液蛋白基因启动子的首次报道。
