DenBoer Lisa M, Hardy-Smith Philip W, Hogan Melissa R, Cockram Gregory P, Audas Timothy E, Lu Rui
Department of Molecular and Cellular Biology, University of Guelph, Ont., Canada N1G 2W1.
Biochem Biophys Res Commun. 2005 May 27;331(1):113-9. doi: 10.1016/j.bbrc.2005.03.141.
Luman (or LZIP, CREB3) is a transcription factor with an endoplasmic reticulum (ER)-transmembrane domain. Due to its structural similarities with ATF6, it is thought that Luman might also be involved in cellular stress responses. Here we report that Luman can bind and activate transcription from the consensus unfolded protein response element (UPRE). Mutations that disrupted the binding of Luman to the UPREs impaired its ability to activate transcription from these sites. Overexpression of Luman stimulated transcription of EDEM, a downstream effector of the mammalian unfolded protein response involved in ER-associated degradation (ERAD). Unlike ATF6, however, Luman was not activated by proteolytic cleavage in response to endoplasmic reticulum stressors such as tunicamycin and thapsigargin. These results suggest that the activation of ERAD by Luman is likely through a pathway different from the common ER stress response, and that additional factor(s) are required for the activation of this Luman-mediated pathway.
鲁曼（或LZIP、CREB3）是一种具有内质网（ER）跨膜结构域的转录因子。由于其与ATF6在结构上相似，人们认为鲁曼可能也参与细胞应激反应。在此我们报告，鲁曼能够结合并激活共有未折叠蛋白反应元件（UPRE）的转录。破坏鲁曼与UPRE结合的突变损害了其从这些位点激活转录的能力。鲁曼的过表达刺激了EDEM的转录，EDEM是哺乳动物未折叠蛋白反应的下游效应因子，参与内质网相关降解（ERAD）。然而，与ATF6不同，鲁曼不会因衣霉素和毒胡萝卜素等内质网应激源而通过蛋白水解切割被激活。这些结果表明，鲁曼对ERAD的激活可能通过一条不同于常见内质网应激反应的途径，并且该鲁曼介导的途径的激活需要其他因子。
