Institute of Neurobiology and Molecular Medicine, CNR, 00133 Rome, Italy.
J Biol Chem. 2010 Apr 30;285(18):13607-15. doi: 10.1074/jbc.M109.082693. Epub 2010 Feb 25.
Heat shock factor-1 (HSF1) is the central regulator of heat-induced transcriptional responses leading to rapid expression of molecular chaperones that protect mammalian cells against proteotoxic stress. The main targets for HSF1 are specific promoter elements (HSE) located upstream of heat shock genes encoding a variety of heat shock proteins, including HSP70, HSP90, HSP27, and other proteins of the network. Herein we report that the zinc finger AN1-type domain-2a gene, also known as AIRAP, behaves as a canonical heat shock gene, whose expression is temperature-dependent and strictly controlled by HSF1. Transcription is triggered at temperatures above 40 degrees C in different types of human cancer and primary cells, including peripheral blood monocytes. As shown by ChIP analysis, HSF1 is recruited to the AIRAP promoter rapidly after heat treatment, with a kinetics that parallels HSP70 promoter HSF1-recruitment. In transfection experiments HSF1-silencing abolished heat-induced AIRAP promoter-driven transcription, which could be rescued by exogenous Flag-HSF1 expression. The HSF1 binding HSE sequence in the AIRAP promoter critical for heat-induced transcription was identified. Because its expression is induced at febrile temperatures in human cells, AIRAP may represent a new potential component of the protective response during fever in humans.
热休克因子-1 (HSF1) 是热诱导转录反应的中央调节因子，导致快速表达分子伴侣，保护哺乳动物细胞免受蛋白毒性应激。HSF1 的主要靶标是位于热休克基因上游的特定启动子元件 (HSE)，这些基因编码各种热休克蛋白，包括 HSP70、HSP90、HSP27 和网络中的其他蛋白质。在此，我们报告锌指 AN1 型结构域-2a 基因，也称为 AIRAP，表现为一种典型的热休克基因，其表达依赖于温度，并且受到 HSF1 的严格控制。在不同类型的人类癌症和原代细胞，包括外周血单核细胞中，转录在 40 度以上的温度下被触发。如 ChIP 分析所示，在热处理后，HSF1 迅速被募集到 AIRAP 启动子，其动力学与 HSP70 启动子 HSF1 募集的动力学平行。在转染实验中，HSF1 沉默消除了热诱导的 AIRAP 启动子驱动的转录，通过外源性 Flag-HSF1 表达可以挽救这种转录。确定了 AIRAP 启动子中对热诱导转录至关重要的 HSF1 结合 HSE 序列。由于其在人类细胞中的表达在发热时被诱导，因此 AIRAP 可能代表人类发热时保护反应的一个新的潜在组成部分。
