11 SUMOylation of LEDGF/p75 Influences Its Transcriptional Activity

Wednesday, November 4, 2009
Ballroom A+B (Camino Real Hotel)
Murilo T. D. Bueno , Biological Sciences, University of Texas at El Paso, El Paso, TX
Jose A. Garcia , Biological Sciences, University of Texas at El Paso, El Paso, TX
Elisa Morales , Biological Sciences, University of Texas at El Paso, El Paso, TX
Jeffrey Kugelman , Biological Sciences, University of Texas at El Paso, El Paso, TX
German Rosas-Acosta , Biological Sciences, University of Texas at El Paso, El Paso, TX
Manuel Llano , Biological Sciences, University of Texas at El Paso, El Paso, TX
Lens epithelium-derived growth factor (LEDGF) proteins, p75 and p52, were firstly identified as transcriptional coactivators that link sequence-specific activators to the basal transcription machinery. These chromatin-bound proteins are generated from alternatively spliced products of the human PC4 and SFRS1 interacting protein 1(PSIP1) gene and share the same N-terminal region composed of 325 amino acid residues. The unique C-terminal regions are 8 amino acids long in LEDGF/p52 and 205 amino acids long in LEDGF/p75. Over-expression of LEDGF/p75 was found to augment transcription of a set of stress-related genes that include heat shock protein 27, αB-crystallin, antioxidant protein 2A and involucrin. Additionally, cells lacking LEDGF/p75 were shown to be markedly resistant to lentiviral infection, including HIV-1. Here, we demonstrate that both LEDGF/p52 and LEDGF/p75 are SUMOylated by SUMO-1 and SUMO-3. SUMOylation is a reversible type of post-translational modification in which a small ubiquitin-like modifier (SUMO) is covalently attached to the ε-amino group of lysine residues. Several transcriptional regulators, including transcription factors, chromatin remodeling proteins and transcriptional co-activators, have been demonstrated to be SUMO targets. SUMOylation of these proteins was shown to influence their localization, activity, stability and molecular partners. Four lysine residues were identified as the major SUMOylation sites in LEDGF proteins. Moreover, mutation of these lysine residues to arginine drastically impaired LEDGF SUMOylation and enhanced the transcriptional activity of LEDGF/p75.
See more of: Wednesday Poster Session
See more of: Abstract Submission