BACKGROUND Propofol exposure to neurons during synaptogenesis results in apoptosis, leading to cognitive dysfunction in adulthood. Previous work from our laboratory showed that isoflurane neurotoxicity occurs through p75 neurotrophin receptor (p75(NTR)) and subsequent cytoskeleton depolymerization. Given that isoflurane and propofol both suppress neuronal activity, we hypothesized that propofol...

LEDGF/p75 interacts with DNA/protein to regulate gene expression and function. Despite the recognized diversity of function of LEDGF/p75, knowledge of its transregulation is in its infancy. Here we report that LEDGF/p75 gene is TATA-less, contains GC-rich cis elements and is transcriptionally regulated by Sp1 involving small ubiquitin-like modifier (Sumo1). Using different cell lines, we showed...

Previous studies demonstrated changes in urinary bladder neurotrophin content and upregulation of neurotrophin receptors, TrkA and the p75 neurotrophin receptor (p75(NTR)), in micturition reflex pathways after cyclophosphamide (CYP)-induced cystitis. p75(NTR) can bind nerve growth factor (NGF) and modulate NGF-TrkA binding and signaling. We examined p75(NTR) expression and the role of p75(NTR) ...

Transcriptional co-activator p75 is implicated in human cancer, autoimmunity and replication of human immunodeficiency virus type 1 (HIV-1) as a dominant integrase-interacting protein. Although characterized as chromatin associated, the normal biological role(s) of p75 remains fairly unclear. To gain insight into p75 function, we have characterized its cellular binding partners and report that ...

Lens epithelium-derived growth factor (LEDGF/p75) is a transcriptional co-activator involved in targeting human immunodeficiency virus (HIV) integration and the development of MLL fusion-mediated acute leukemia. A previous study revealed that LEDGF/p75 dynamically scans the chromatin, and upon interaction with HIV-1 integrase, their complex is locked on chromatin. At present, it is not known wh...

Rod photoreceptors are susceptible to light-induced cell death. Previous results have suggested that the neurotrophin receptor p75 in Müller cells controls photoreceptor cell death during light-exposure by suppressing trophic factor release; and consequently, if p75 is blocked or eliminated during light-exposure, apoptosis is delayed. We explored this question by examining photoreceptor cell su...

The neurotrophin receptor p75 is induced by various injuries to the nervous system, but its role after injury has remained unclear. Here, we report that p75 is required for the death of oligodendrocytes following spinal cord injury, and its action is mediated mainly by proNGF. Oligodendrocytes undergoing apoptosis expressed p75, and the absence of p75 resulted in a decrease in the number of apo...

The p75 neurotrophin receptor (p75(NTR)) interacts with multiple ligands and coreceptors. It is thought to mediate myelin growth inhibition as part of the Nogo receptor complex, in addition to its other roles. Paradoxically, however, peripheral axons of p75(ExonIII-/-) mutant embryos are severely stunted. This inhibition of axon growth may be a result of neurite elongation defects in p75(NTR) m...

The p75 neurotrophin receptor, a member of the tumor necrosis factor receptor superfamily, is required as a co-receptor for the Nogo receptor (NgR) to mediate the activity of myelin-associated inhibitors such as Nogo, MAG, and OMgp. p45/NRH2/PLAIDD is a p75 homologue and contains a death domain (DD). Here we report that p45 markedly interferes with the function of p75 as a co-receptor for NgR. ...

Background Via its interaction with the cellular cofactor LEDGF/p75, HIV-1 integration is targeted towards active genes. Several strategies were used to show the important role of LEDGF/p75 in viral replication. After RNAi-mediated knockdown of LEDGF/p75, residual replication was observed, possibly supported by minute LEDGF/p75 protein levels. Mouse knockout fibroblasts were generated, enabling...