Singh D P, Fatma N, Kimura A, Chylack L T, Shinohara T
Center for Ophthalmic Research, Department of Ophthalmology, Harvard Medical School, 221 Longwood Avenue, Boston, Massachusetts 02115, USA.
Biochem Biophys Res Commun. 2001 May 18;283(4):943-55. doi: 10.1006/bbrc.2001.4887.
We have investigated the mechanism by which LEDGF protects cells against environmental stress. Our earlier report showed that a low level of LEDGF was present in the nucleus of most cell types and significant elevation of LEDGF level was induced by heat and oxidative stress. The cells overexpressing LEDGF-activated expression of heat shock proteins and enhanced survival of many cell types. Here we show that LEDGF binds to heat shock element (HSE) and stress-related regulatory element (STRE) to activate the expression of stress-related genes (Hsp27 and alphaB-crystallin). Apparently, HSE and STRE are present in promoters of many stress-related genes. Elevation of many stress-related proteins (STRPs) induced by LEDGF may protect cells against environmental stress. In yeast, it has been demonstrated that a single stress can activate the expression of multiple STRPs. This is known as "cross-protection," and now similar mechanism has been found in mammalian cells and LEDGF plays a vital role in it.
我们已经研究了LEDGF保护细胞免受环境应激的机制。我们早期的报告显示，大多数细胞类型的细胞核中存在低水平的LEDGF，并且热应激和氧化应激会诱导LEDGF水平显著升高。过表达LEDGF的细胞激活了热休克蛋白的表达，并提高了多种细胞类型的存活率。在此我们表明，LEDGF与热休克元件（HSE）和应激相关调节元件（STRE）结合，以激活应激相关基因（Hsp27和αB-晶状体蛋白）的表达。显然，HSE和STRE存在于许多应激相关基因的启动子中。LEDGF诱导的多种应激相关蛋白（STRPs）水平升高可能保护细胞免受环境应激。在酵母中，已经证明单一应激可以激活多种STRPs的表达。这被称为“交叉保护”，现在在哺乳动物细胞中也发现了类似的机制，并且LEDGF在其中起着至关重要的作用。
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