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Direct Regulation Of Apoptosis By Linear Ubiqutin Chain Assembly Complex (Lubac) And Feedback Regulation Of Lubac Function By Caspases, Donghyun Joo
Dissertations & Theses (Open Access)
Tumor Necrosis Factor-alpha (TNF-α) is a cytokine that plays a role in various cellular processes such as proliferation, differentiation (mainly through NF-κB signaling) and death (via apoptosis signaling). Recently, linear ubiquitination by LUBAC (linear ubiquitin chain assembly complex) was reported to have a regulatory function in TNF-α mediated NF-κB activation. Although LUBAC is suggested to control not only NF-kB signaling but also the apoptosis pathway, the precise mechanism of apoptosis regulation remains unknown. Moreover, NF-κB and apoptosis pathways have opposed but fundamental functions for various cellular processes. Although these two pathways actively interplay to balance the death and survival, the …
Rest Regulatory Circuit Controls Distinct Oncogenic Properties Of Glioblastoma Stem Cells Through Specific Micrornas, Anantha L Marisetty
Rest Regulatory Circuit Controls Distinct Oncogenic Properties Of Glioblastoma Stem Cells Through Specific Micrornas, Anantha L Marisetty
Dissertations & Theses (Open Access)
Glioblastoma Multiforme (GBM) is the most common and aggressive primary malignant brain tumor in adults. With an average survival of only 12-16 months the prognosis for GBM patients remains dismal, with less than 5% of patients surviving 5 years. New mechanism-based approaches are necessary for the management of patients with GBM. Many GBM tumors are believed to be caused by self-renewing, glioblastoma-derived stem-like cells (GSCs). These GSCs are resistant to chemo- and radiation therapies, and are believed to be responsible for tumor recurrence. In a recent paper from our lab we have shown that REST, RE1-silencing transcription factor, regulates oncogenic …
Induction Of Caspase-Dependent Death By Proteasome Targeted Therapy In Glioblastoma, Christa A. Manton
Induction Of Caspase-Dependent Death By Proteasome Targeted Therapy In Glioblastoma, Christa A. Manton
Dissertations & Theses (Open Access)
New therapeutic options are needed for glioblastoma, a deadly disease with a median survival of only 14 months with current treatment. The proteasome inhibitor bortezomib (BTZ) shows efficacy in cancers like myeloma, but its clinical utility in other cancer types has been more limited. Newer proteasome inhibitors such as marizomib (MRZ) have unique inhibitory and death inducing properties that have not been well examined in GBM. Additionally, targeting other components of the ubiquitin-proteasome system is possible, but has not been explored in GBM. Questions also still remain about the ability of BTZ and MRZ to be delivered to brain tumors …