Molecular Biology Commons^™

The Role Of Cyp33 In Mll Mediated Gene Repression, Steven D. Poppen

Dissertations

Mixed Lineage Leukemia (MLL) is a multidomain protein whose gene is translocated in a subset of AML leukemias. Translocation of the MLL gene is present in approximately five percent of adult acute leukemias and ten percent of pediatric leukemias (Daser, A 2004, Look, A 1997, Huret, J 2001) Patients presenting in the clinic at the time of diagnosis with an MLL fusion have been shown to respond poorly to treatment and have a worse prognosis than matched wild type MLL patients (Rubnitz, J 1994, Rubnitz, J 1999). Novel therapies therefore are needed in order to more effectively treat patients with …

Molecular Mechanisms Regulating Chemokine Receptor Cxcr4 Signaling And Trafficking, Rohit Malik

Dissertations

CXCR4 is a G protein-coupled receptor (GPCR) that binds to the chemokine, stromal cell-derived factor-1 (SDF-1alpha; a.k.a. CXCL12). The SDF-1alpha/CXCR4 signaling axis plays an essential role during embryogenesis in the development of the heart, brain and vasculature and in the adult mediating immune cell trafficking and stem cell homing to the bone marrow. Dysregulation of SDF-1alpha/CXCR4 signaling is linked to several pathological conditions, including cardiovascular disease, immunological disorders as well as cancer growth and metastasis. However, the mechanisms that govern CXCR4 signaling remain poorly understood. In this dissertation project, we attempt to further our understanding of the molecular mechanisms that …

Determination Of An Interaction Between Nipped B-Like Protein And Mll, Adam Robert Marek

Master's Theses

The Mixed Lineage Leukemia (MLL) protein serves as a positive transcriptional regulator during hematopoietic and embryonic development. The MLL gene can undergo chromosomal translocations producing leukemia-causing fusions that retain the MLL amino-terminus, including the repression domain. A recent yeast two-hybrid screening used the MLL repression domain as bait and yielded nine positive clones of Nipped B-like (NIPBL).

NIPBL is a crucial member of the cohesin complex, which functions in the segregation of sister chromatids during cell division. However, recent evidence suggests the cohesin complex can also function as a transcriptional regulator.

In this study, we wanted to confirm this interaction …

Characterization Of The Coca Chemokine Receptor Four Agonist Activity Of Ubiquitin, Daniel M. Staren

Master's Theses

Ubiquitin has previously been identified as another natural agonist of CXC chemokine receptor 4 (CXCR4). In addition, recent evidence suggests that ubiquitin may activate CXCR4 through a binding site on the receptor, which is distinct from the binding site for the cognate ligand stromal cell-derived factor (SDF)-1α. The cellular consequences of ubiquitin induced CXCR4 activation, however, are still poorly defined and a side-by-side comparison of CXCR4 mediated functions after activation with SDF-1α and ubiquitin is lacking. Such information will be instrumental to better understand the physiological function of CXCR4 and to further define its role as a therapeutic target in …