Early growth response genes (Egr1-4) are induced as immediate early genes by a variety of extracellular stimuli that influence cellular growth and differentiation. Egr transcriptional regulators modulate gene expression by binding to Egr response elements (ERE) in target genes. In this study, the low affinity p75 neurotrophin receptor (p75NTR) was...
Barbed end regulation is critical to the formation of the actin-based protrusive structures, lamellipodia and filopodia. In this body of work we have chosen to focus on two main activities, filament termination by the heterodimeric Capping protein (CP) and continued filament elongation by the Ena/VASP family of proteins. We demonstrate...
Prostate cancer (PCa) is the most commonly diagnosed cancer (1:6), and the second most common cause of cancer-related deaths in American men (>27,000/year). Metastasis is largely responsible for these deaths. During metastasis, tumor cells travel from the prostate to a distant organ where they establish a secondary tumor. Cell motility...
Multiple Myeloma (MM) is an incurable plasma cell malignancy occurring within the bone marrow. Glucocorticoids (GCs) are widely used in the treatment of MM patients due to potent induction of apoptosis. Though known to occur via the glucocorticoid receptor (GR), the molecular details of GC-induced apoptosis in MM cells remain...
The response to reduced levels of oxygen (hypoxia) is essential for embryonic development by promoting the proper formation of vascular networks. Conversely, hypoxia also promotes the development of pathophysiological processes such as pulmonary hypertension and cancer. The main mediator of responses to hypoxia within the cell is the transcription factor...
Breast cancer cells acquire many genetic alterations in apoptotic signaling pathways rendering them resistant to apoptosis. Human Epidermal growth factor Receptor-2 (HER-2/ErbB2/neu) is amplified or overexpressed in approximately 30% of breast and ovarian tumors and correlates with poor prognosis. Although HER-2 is an orphan receptor, it forms potent signaling heterodimers...
Initial studies described the ability of CD4+CD25+ T regulatory (Treg) cells in suppressing autoimmune diseases in animal models. An emerging interest has focused on the potential role of Treg cells in cancer development and progression as they have been shown to suppress anti-tumor immunity. In the present study, CD4+CD25- T...
The ubiquitin-proteasome system degrades regulatory proteins and thereby controls a broad range of cellular processes such as the cell cycle, DNA-repair, gene transcription and signal transduction. The proteasome typically degrades its substrates completely into small peptides. However, biological exceptions do occur. For example, the activity of a handful of transcriptional...
Epstein-Barr virus (EBV) is a human gamma-herpesvirus that primarily infects B cells and epithelial cells. While the glycoproteins required for entry into these two cell types differ, the gH/gL glycoprotein complex is essential for entry into both epithelial and B cells. Analysis of gH protein sequences from three gamma-herpesviruses: EBV,...
It is critical to genomic integrity that DNA is replicated completely and faithfully during each cell cycle. The essential replication factor Cdt1 is a critical protein in preventing reinitiation of replication. Overexpression of Cdt1 causes re-replication in p53 null cells and transforms NIH3T3 cells, causing them to form tumors in...