Life Sciences Commons^™

Determining The Roles Of The Oligomerization And C-Terminal Domains In Mutant P53 Gain-Of-Function Activities, George K. Annor

Dissertations, Theses, and Capstone Projects

The tumor suppressor p53 (TP53) gene is often mutated in cancer, with missense mutations found in the central DNA binding domain, and less often in the oligomerization domain (OD) and C-terminal domain (CTD). The OD and CTD have been found to be critical for the tumor suppressor functionality of wild-type p53 (wtp53). Specific missense mutations in the DNA binding domain have been found to confer new gain-of-function (GOF) activities. Mutations that destabilize tetramer formation, or deletion of key lysine residues within the CTD, downregulate the ability of wtp53 to transactivate (increase the rate of transcription of) its target …

Functional Interactions Of Tau, Pin1, P53 And Mrna 3′ Processing Factors In Non-Neuronal Cells, Jorge E. Baquero

Dissertations, Theses, and Capstone Projects

ABSTRACT

mRNA 3’ end processing, an essential step in eukaryotic RNA metabolism, regulates the steady-state levels of different mRNAs and contributes to the cells rapid response to stress. Studies have described potential contributions of mRNA 3’ end processing to numerous human diseases, including cancer and Alzheimer’s disease (AD). Therefore, the main purpose of this dissertation is to further elucidate some of the roles of disease-related factors Pin1, p53 and tau in the regulation mRNA 3’ end processing in non-neuronal cells under different cellular conditions, including during the DNA damage response (DDR).

The results from Chapter II show that the prolyl …

The Role Of Mdm2 In Dna Damage Signaling, Stanley Tam

Theses and Dissertations

The overexpression of the oncogene MDM2 is common in a variety of human cancers. MDM2 overexpression is known to increase genome instability in cells by delaying DNA double strand break repair and γH2AX levels. This study explores the knockdown of MDM2 and how it may affect DNA damage signaling.

The Role Of Nucleolin Phosphorylation By Ck2 In Regulating Cellular Fate Under Normal And Stress Conditions, Shu Xiao

Dissertations, Theses, and Capstone Projects

Nucleolin (NCL or C23) is an abundant genotoxic stress-responsive RNA binding phosphoprotein. NCL constitutes 10% of total nucleolar protein that has functions in multiple biological processes, including ribosome biogenesis, DNA/RNA metabolism, cellular response to DNA damage, cell growth, proliferation and death. In this dissertation, I elucidate the role of nucleolin phosphorylation by casein kinase 2 (CK2) in controlling cellular fate by regulating p53 checkpoint under normal and stressed conditions. First, I demonstrate that the six consensus CK2 sites on the N-terminus of NCL are important for cell survival and proliferation. Expression of CK2 phosphorylation-deficient NCL mutant leads to dominant negative …