Sasaki Kanae, Komori Ryota, Taniguchi Mai, Shimaoka Akie, Midori Sachiko, Yamamoto Mayu, Okuda Chiho, Tanaka Ryuya, Sakamoto Miyu, Wakabayashi Sadao, Yoshida Hiderou
Department of Molecular Biochemistry, Graduate School of Life Science, University of Hyogo.
Cell Struct Funct. 2019 Jan 11;44(1):1-19. doi: 10.1247/csf.18031. Epub 2018 Nov 28.
The Golgi stress response is a homeostatic mechanism that augments the functional capacity of the Golgi apparatus when Golgi function becomes insufficient (Golgi stress). Three response pathways of the Golgi stress response have been identified in mammalian cells, the TFE3, HSP47 and CREB3 pathways, which augment the capacity of specific Golgi functions such as N-glycosylation, anti-apoptotic activity and pro-apoptotic activity, respectively. On the contrary, glycosylation of proteoglycans (PGs) is another important function of the Golgi, although the response pathway upregulating expression of glycosylation enzymes for PGs in response to Golgi stress remains unknown. Here, we found that expression of glycosylation enzymes for PGs was induced upon insufficiency of PG glycosylation capacity in the Golgi (PG-Golgi stress), and that transcriptional induction of genes encoding glycosylation enzymes for PGs was independent of the known Golgi stress response pathways and ER stress response. Promoter analyses of genes encoding these glycosylation enzymes revealed the novel enhancer elements PGSE-A and PGSE-B (the consensus sequences are CCGGGGCGGGGCG and TTTTACAATTGGTC, respectively), which regulate their transcriptional induction upon PG-Golgi stress. From these observations, the response pathway we discovered is a novel Golgi stress response pathway, which we have named the PG pathway.Key words: Golgi stress, proteoglycan, ER stress, organelle zone, organelle autoregulation.
高尔基体应激反应是一种稳态机制，当高尔基体功能不足（高尔基体应激）时，它会增强高尔基体的功能能力。在哺乳动物细胞中已鉴定出高尔基体应激反应的三种反应途径，即TFE3、HSP47和CREB3途径，它们分别增强特定高尔基体功能的能力，如N-糖基化、抗凋亡活性和促凋亡活性。相反，蛋白聚糖（PGs）的糖基化是高尔基体的另一项重要功能，尽管响应高尔基体应激上调PGs糖基化酶表达的反应途径尚不清楚。在这里，我们发现，当高尔基体中PG糖基化能力不足（PG-高尔基体应激）时，PGs糖基化酶的表达会被诱导，并且编码PGs糖基化酶的基因的转录诱导独立于已知的高尔基体应激反应途径和内质网应激反应。对编码这些糖基化酶的基因进行启动子分析，发现了新的增强子元件PGSE-A和PGSE-B（共有序列分别为CCGGGGCGGGGCG和TTTTACAATTGGTC），它们在PG-高尔基体应激时调节其转录诱导。基于这些观察结果，我们发现的反应途径是一种新的高尔基体应激反应途径，我们将其命名为PG途径。关键词：高尔基体应激；蛋白聚糖；内质网应激；细胞器区；细胞器自调节。
