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Articles 1 - 7 of 7

Full-Text Articles in Biochemistry, Biophysics, and Structural Biology

Characterization Of The Rna Binding And Rna Degrading Subunits Of The Eukaryotic Exosome, Borislava Tsanova Dec 2013

Characterization Of The Rna Binding And Rna Degrading Subunits Of The Eukaryotic Exosome, Borislava Tsanova

UT GSBS Dissertations and Theses (Open Access)

The exosome is an essential complex of ten proteins involved in the processing and degradation of many RNAs in the cell. These include various stable RNAs, mRNAs, and aberrant transcripts both in the nucleus and in the cytoplasm.

In this work I characterize the three members of the exosome “cap”, the RNA binding proteins Rrp4, Rrp40, and Csl4. I determine that in spite of their structural similarity, they each have a unique essential role. Second, I determine that two of the cap proteins Rrp4 and Rrp40 have a role in bridging subunits of the PH ring of the exosome. The ...


Studying Aggregate Formation By Amyotrophic Lateral Sclerosis-Associated Mutant Sod1 Protein In Drosophila Model, Michael Mccarthy Aug 2013

Studying Aggregate Formation By Amyotrophic Lateral Sclerosis-Associated Mutant Sod1 Protein In Drosophila Model, Michael Mccarthy

UT GSBS Dissertations and Theses (Open Access)

A common pathological hallmark of most neurodegenerative disorders is the presence of protein aggregates in the brain. Understanding the regulation of aggregate formation is thus important for elucidating disease pathogenic mechanisms and finding effective preventive avenues and cures. Amyotrophic Lateral Sclerosis (ALS), also known as Lou Gehrig’s disease, is a selective neurodegenerative disorder predominantly affecting motor neurons. The majority of ALS cases are sporadic, however, mutations in superoxide dismutase 1 (SOD1) are responsible for about 20% of familial ALS (fALS). Mutated SOD1 proteins are prone to misfold and form protein aggregates, thus representing a good candidate for studying aggregate ...


Characterization Of Jak, Stat, And Src Interactions In Head And Neck Squamous Cell Carcinoma, Reshma Jaseja, Reshma Jaseja Aug 2013

Characterization Of Jak, Stat, And Src Interactions In Head And Neck Squamous Cell Carcinoma, Reshma Jaseja, Reshma Jaseja

UT GSBS Dissertations and Theses (Open Access)

Recurrence of Head and Neck Squamous Cell Carcinoma (HNSCC) is common; thus, it is essential to improve the effectiveness and reduce toxicity of current treatments. Proteins in the Src/Jak/STAT pathway represent potential therapeutic targets, as this pathway is hyperactive in HNSCC and it has roles in cell migration, metastasis, proliferation, survival, and angiogenesis. During short-term Src inhibition, Janus kinase (Jak) 2, and signal transducer and activator of transcription (STAT) 3 and STAT5 are dephosphorylated and inactivated. Following sustained Src inhibition, STAT5 remains inactive, but Jak2 and STAT3 are reactivated following their early inhibition. To further characterize the mechanism ...


Mechanisms Underlying The Heterogeneous Sensitivities Of Cancer Cells To Proteasome Inhibitors, Matthew C. White May 2013

Mechanisms Underlying The Heterogeneous Sensitivities Of Cancer Cells To Proteasome Inhibitors, Matthew C. White

UT GSBS Dissertations and Theses (Open Access)

The mechanisms underlying cellular response to proteasome inhibitors have not been clearly elucidated in solid tumor models. Evidence suggests that the ability of a cell to manage the amount of proteotoxic stress following proteasome inhibition dictates survival. In this study using the FDA-approved proteasome inhibitor bortezomib (Velcade®) in solid tumor cells, we demonstrated that perhaps the most critical response to proteasome inhibition is repression of global protein synthesis by phosphorylation of the eukaryotic initiation factor 2-α subunit (eIF2α). In a panel of 10 distinct human pancreatic cancer cells, we showed marked heterogeneity in the ability of cancer cells to induce ...


Structure-Function Analysis Of Human Integrator Subunit-4, Anupama Sataluri May 2013

Structure-Function Analysis Of Human Integrator Subunit-4, Anupama Sataluri

UT GSBS Dissertations and Theses (Open Access)

Structure-function analysis of human Integrator subunit 4

Anupama Sataluri

Advisor: Eric. J. Wagner, Ph.D.

Uridine-rich small nuclear RNAs (U snRNA) are RNA Polymerase-II (RNAPII) transcripts that are ubiquitously expressed and are known to be essential for gene expression. snRNAs play a key role in mRNA splicing and in histone mRNA expression. Inaccurate snRNA biosynthesis can lead to diseases related to defective splicing and histone mRNA expression. Although the 3′ end formation mechanism and processing machinery of other RNAPII transcripts such as mRNA has been well studied, the mechanism of snRNA 3′ end processing has remained a mystery until the ...


Genome-Wide Profiling Unveils Criticial Functions Of P53 In Human Embryonic Stem Cells, Kadir C. Akdemir May 2013

Genome-Wide Profiling Unveils Criticial Functions Of P53 In Human Embryonic Stem Cells, Kadir C. Akdemir

UT GSBS Dissertations and Theses (Open Access)

Embryonic stem cells (ESCs) possess two unique characteristics: infinite self-renewal and the potential to differentiate into almost every cell type (pluripotency). Recently, global expression analyses of metastatic breast and lung cancers revealed an ESC-like expression program or signature, specifically for cancers that are mutant for p53 function. Surprisingly, although p53 is widely recognized as the guardian of the genome, due to its roles in cell cycle checkpoints, programmed cell death or senescence, relatively little is known about p53 functions in normal cells, especially in ESCs. My hypothesis is that p53 has specific transcription regulatory functions in human ESCs (hESCs) that ...


Interaction Between Brk And Her2 In Breast Cancer, Midan Ai May 2013

Interaction Between Brk And Her2 In Breast Cancer, Midan Ai

UT GSBS Dissertations and Theses (Open Access)

INTERACTION BETWEEN BRK AND HER2 IN BREAST CANCER

Midan Ai, Ph.D.

Supervisory Professor: Zhen Fan, M.D.

Breast tumor kinase (Brk) is a nonreceptor protein-tyrosine kinase that is highly expressed in approximately two thirds of breast cancers but is not detectable or is expressed at very low levels in normal mammary epithelium. Brk plays important roles in promoting proliferation, survival, invasion, and metastasis of breast cancer cells, but the mechanism(s) of which remain largely unknown. Recent studies showed that Brk is frequently co-overexpressed with human epidermal growth factor receptor-2 (HER2) and is physically associated with HER2 in breast ...