Department of Medicine, University of Wisconsin-Madison, Madison, WI 53705, USA.
J Cell Sci. 2010 Oct 1;123(Pt 19):3378-88. doi: 10.1242/jcs.068841. Epub 2010 Sep 7.
The transient or permanent modification of nascent proteins in the early secretory pathway is an essential cellular function that ensures correct folding and maturation of membrane and secreted proteins. We have recently described a new form of post-translational regulation of the membrane protein β-site APP cleaving enzyme 1 (BACE1) involving transient lysine acetylation in the lumen of the endoplasmic reticulum (ER). The essential components of this process are two ER-based acetyl-CoA:lysine acetyltransferases, ATase1 and ATase2, and a membrane transporter that translocates acetyl-CoA into the lumen of the ER. Here, we report the functional identification of acetyl-CoA transporter 1 (AT-1) as the ER membrane acetyl-CoA transporter. We show that AT-1 regulates the acetylation status of ER-transiting proteins, including the membrane proteins BACE1, low-density lipoprotein receptor and amyloid precursor protein (APP). Finally, we show that AT-1 is essential for cell viability as its downregulation results in widespread cell death and induction of features characteristic of autophagy.
在早期分泌途径中新生蛋白质的瞬时或永久修饰是一种重要的细胞功能，可确保膜和分泌蛋白的正确折叠和成熟。我们最近描述了一种新的跨膜蛋白β-位点 APP 切割酶 1（BACE1）的翻译后调节形式，涉及内质网（ER）腔中赖氨酸的瞬时乙酰化。该过程的基本组成部分是两种基于 ER 的乙酰辅酶 A：赖氨酸乙酰转移酶，ATase1 和 ATase2，以及一种将乙酰辅酶 A 转运到 ER 腔中的膜转运蛋白。在这里，我们报告了将乙酰辅酶 A 转运蛋白 1（AT-1）鉴定为 ER 膜乙酰辅酶 A 转运蛋白的功能。我们表明，AT-1 调节包括 BACE1、低密度脂蛋白受体和淀粉样前体蛋白（APP）在内的 ER 易位蛋白的乙酰化状态。最后，我们表明 AT-1 对细胞活力至关重要，因为其下调会导致广泛的细胞死亡和自噬特征的诱导。
