title: LEDGF binds to heat shock and stress-related element to activate the expression of stress-related genes.
abstract: 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.
authors.affiliation: Center for Ophthalmic Research, Department of Ophthalmology, Harvard Medical School, 221 Longwood Avenue, Boston, Massachusetts 02115, USA.
authors.forename: D P
authors.initials: DP
authors.lastname: Singh
authors.forename: N
authors.initials: N
authors.lastname: Fatma
authors.forename: A
authors.initials: A
authors.lastname: Kimura
authors.forename: L T
authors.initials: LT
authors.lastname: Chylack
authors.forename: T
authors.initials: T
authors.lastname: Shinohara
mesh_terms: D001483:Base Sequence; D003459:Crystallins / Q000235:genetics; D004247:DNA; D015536:Down-Regulation; D005786:Gene Expression Regulation; D006133:Growth Substances / Q000737:chemistry / Q000378:metabolism*; D006360:Heat-Shock Proteins / Q000235:genetics / Q000378:metabolism*; D036341:Intercellular Signaling Peptides and Proteins; D018384:Oxidative Stress; D011401:Promoter Regions, Genetic; D011485:Protein Binding; D012689:Sequence Homology, Nucleic Acid; D015533:Transcriptional Activation
chemical_list: D003459:Crystallins; D006133:Growth Substances; D006360:Heat-Shock Proteins; D036341:Intercellular Signaling Peptides and Proteins; C119380:lens epithelium-derived growth factor; D004247:DNA