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Regulation Of The Tumor Suppresser P53 And Survivin By Ras And Ral Gtpases:Implications For Malignant Transformation, Awet G. Tecleab Jan 2013

Regulation Of The Tumor Suppresser P53 And Survivin By Ras And Ral Gtpases:Implications For Malignant Transformation, Awet G. Tecleab

Graduate Theses and Dissertations

Abstract

Although the critical role of the small GTPases Ras and Ral in oncogenesis has been well documented, much remains to be investigated about the molecular mechanism by which these GTPases regulate malignant transformation. The work under this thesis made two major contributions to this field. The first is the discovery that K-Ras, RalA and/or RalB are required for the maintenance of the high levels of the anti-apoptotic protein survivin in some human cancer cells, and the second is the demonstration that down regulation of K-Ras, RalA and/or RalB, but not Raf-1 or Akt1/2, stabilizes the tumor ...


Functional And Mutational Analysis Of Human Recq-Like Dna Helicases In Saccharomyces Cerevisiae, Hamed Mirzaei-Souderjani Jan 2013

Functional And Mutational Analysis Of Human Recq-Like Dna Helicases In Saccharomyces Cerevisiae, Hamed Mirzaei-Souderjani

Graduate Theses and Dissertations

RecQ-like proteins are a family of DNA helicases that are evolutionary conserved from prokaryotes to eukaryotes. A large amount of experimental evidence suggests these proteins have a major role in the maintenance of genome stability. In humans five RecQ like helicase have been identified (RecQL1, BLM, WRN, RecQL4, and RecQL5), three of which are associated with rare genetic disorders with sever chromosomal and developmental abnormalities, and an elevated predisposition to cancer. Among the disease associated RecQ-like helicases, BLM and WRN have been subject to extensive research, while our collective knowledge about the function of RecQL4 is still very limited. Similarly ...


Sirt1 Regulation Of The Heat Shock Response In An Hsf1-Dependent Manner And The Impact Of Caloric Restriction, Rachel Rene Raynes Jan 2013

Sirt1 Regulation Of The Heat Shock Response In An Hsf1-Dependent Manner And The Impact Of Caloric Restriction, Rachel Rene Raynes

Graduate Theses and Dissertations

The heat shock response (HSR) is the cell's molecular reaction to protein damaging stress and is critical in the management of denatured proteins. Activation of HSF1, the master transcriptional regulator of the HSR, results in the induction of molecular chaperones called heat shock proteins (HSPs). Transcription of hsp genes is promoted by the hyperphosphorylation of HSF1, while the attenuation of the HSR is regulated by a dual mechanism involving negative feedback inhibition from HSPs and acetylation at a critical lysine residue within the DNA binding domain of HSF1, which results in a loss of affinity for DNA. SIRT1 is ...


Drug Resistance Mechanisms To Gamma-Secretase Inhibitors In Human Colon Cancer Cells, Cindy R. Timme Jan 2013

Drug Resistance Mechanisms To Gamma-Secretase Inhibitors In Human Colon Cancer Cells, Cindy R. Timme

Graduate Theses and Dissertations

Colorectal cancer is the third leading cause of cancer-related mortality. Much progress has been achieved in combating this disease with surgical resection and chemotherapy in combination with targeted drugs. However, most metastatic patients develop drug resistance so new modalities of treatment are needed.

Notch signaling plays a vital role in intestinal homeostasis, self-renewal, and cell fate decisions during post-development and is activated in colorectal adenocarcinomas. Under debate is its role in carcinomas and metastatic disease. In theory, blocking Notch activation using gamma-secretase inhibitors (GSIs) may show efficacy alone or in combination with chemotherapy in the treatment of colon cancer.

In ...


Phosphorylation Of Histone Deacetylase 6 Within Its C-Terminal Region By Extracellular Signal Regulated Kinase 1, Kendra Allana Williams Jan 2013

Phosphorylation Of Histone Deacetylase 6 Within Its C-Terminal Region By Extracellular Signal Regulated Kinase 1, Kendra Allana Williams

Graduate Theses and Dissertations

http://upload.etdadmin.com/etdadmin/pdfout/222759_supp_undefined_2A63E500-E9D7-11E2-925E-BE522E1BA5B1.PDF


Epigenetic Modifiers To Augment The Immunogenicity Of Chronic Lymphocytic Leukemia, Jason A. Dubovsky Jan 2013

Epigenetic Modifiers To Augment The Immunogenicity Of Chronic Lymphocytic Leukemia, Jason A. Dubovsky

Graduate Theses and Dissertations

Cancer cells employ a litany of immunosuppressive and immunevasive strategies to avoid detection and elimination by the various arms of the innate and adaptive immune system. Many hematologic and solid tumors progressively develop a specialized microenvironment which promotes tissue restructuring inflammation while masking the immune signature of the tumor cells themselves. Chronic lymphocytic leukemia, a malignancy of mature B lymphocytes must constantly balance on the precipice of immune recognition. A mature antigen presenting cell themselves, CLL clonal growth is dependent on the very interactions which, if effective, could potentially lead to their demise. To circumvent this, CLL clones set up ...