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Full-Text Articles in Molecular Biology

The Role Of Ledgf/P75 In Transcriptional Regulation, Jeffrey Ryan Kugelman Jan 2010

The Role Of Ledgf/P75 In Transcriptional Regulation, Jeffrey Ryan Kugelman

Open Access Theses & Dissertations

The Lens Epithelial Derived Growth Factor p75 (LEDGF/p75) is a chromatin bound protein whose cellular function is not yet clearly known. A role in transcriptional regulation had been previously proposed based on its interaction with the basal transcriptional machinery and on its effects on the expression of genes involved in the cellular response to environmental stresses. To further elucidate the function of LEDGF/p75, we conducted a global and unbiased evaluation of the role of this protein in gene expression. To that aim, we performed a microarray analysis of cellular gene expression in cells that are severely depleted of LEDGF/p75. To …


The Role Of Sumoylation Of Ledgf/P75 In Hiv-1 Infection, Murilo Tadeu Domingues Bueno Jan 2010

The Role Of Sumoylation Of Ledgf/P75 In Hiv-1 Infection, Murilo Tadeu Domingues Bueno

Open Access Theses & Dissertations

The lens epithelium-derived growth factor (LEDGF) proteins p75 and p52 are transcriptional co-activators that protect cells from stresses through modulation of stress and heat shock-related genes. Besides regulating such genes, LEDGF/p75 is also important in the process of HOX gene expression and leukemia transformation driven by the MLL histone methyl transferase complex. By exploiting a similar mechanism of interaction between LEDGF/p75 and MLL, the HIV-1 viral protein Integrase (IN) associates with LEDGF/p75 in order to execute efficient viral DNA integration. This present work has identified that LEDGF proteins are posttranslationally modified by SUMO-1 and -3. SUMOylation was found to target …


Evaluating The Role Of Evolutionarily Conserved Regions Of Ledgf/P75 In Hiv-1 Infection, Jose Adrian Garcia Jan 2010

Evaluating The Role Of Evolutionarily Conserved Regions Of Ledgf/P75 In Hiv-1 Infection, Jose Adrian Garcia

Open Access Theses & Dissertations

LEDGF/p75 is an important cellular co-factor for lentiviral integration. LEDGF/p75-deficient cells are markedly resistant to HIV-1 infection and re-expression of the wild type protein rescues infectivity. Although the molecular mechanism of LEDGF/p75 in HIV-1 integration is not yet known, this co-factor activity requires the interaction of LEDGF/p75 with both the host chromatin and viral integrase. In order to evaluate the involvement of other LEDGF/p75 regions in HIV-1 infection we constructed a panel of deletion mutants targeting clusters of charged residues that are evolutionarily conserved and predicted to be post-translationally modified. These mutants were evaluated for their ability to rescue HIV-1 …