Taniguchi Mai, Sasaki-Osugi Kanae, Oku Masaya, Sawaguchi Shogo, Tanakura Soichiro, Kawai Yumeto, Wakabayashi Sadao, Yoshida Hiderou
Department of Molecular Biochemistry, Graduate School of Life Science, University of Hyogo.
Cell Struct Funct. 2016 Jul 30;41(2):93-104. doi: 10.1247/csf.16005. Epub 2016 Jun 2.
The Golgi stress response is a homeostatic mechanism that controls the capacity of the Golgi apparatus in accordance with cellular demands. When the capacity of the Golgi apparatus becomes insufficient (Golgi stress), transcription levels of Golgi-related genes encoding glycosylation enzymes, a Golgi structural protein, and components of vesicular transport are upregulated through a common cis-acting enhancer-the Golgi apparatus stress response element (GASE). Here, we identified the transcription factor MLX as a GASE-binding protein. MLX resides in the cytoplasm and does not bind to GASE in normal growth conditions, whereas MLX translocates into the nucleus and specifically binds to GASE in response to Golgi stress. Suppression of MLX expression increased transcriptional induction of target genes of the Golgi stress response, whereas overexpression of MLX reduced GASE-binding of TFE3 as well as transcriptional induction from GASE, suggesting that MLX is a transcriptional repressor of the mammalian Golgi stress response.
高尔基体应激反应是一种稳态机制，可根据细胞需求控制高尔基体的功能。当高尔基体功能不足（高尔基体应激）时，编码糖基化酶、高尔基体结构蛋白和囊泡运输成分的高尔基体相关基因的转录水平会通过一个共同的顺式作用增强子——高尔基体应激反应元件（GASE）上调。在此，我们鉴定出转录因子MLX为一种GASE结合蛋白。MLX位于细胞质中，在正常生长条件下不与GASE结合，而在高尔基体应激时，MLX会转位到细胞核并特异性结合GASE。抑制MLX表达会增加高尔基体应激反应靶基因的转录诱导，而MLX过表达则会降低TFE3与GASE的结合以及GASE的转录诱导，这表明MLX是哺乳动物高尔基体应激反应的转录抑制因子。
