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Full-Text Articles in Molecular Biology

Investigation Of Alcohol-Induced Changes In Hepatic Histone Modifications Using Mass Spectrometry Based Proteomics, Crystina Leah Kriss Apr 2018

Investigation Of Alcohol-Induced Changes In Hepatic Histone Modifications Using Mass Spectrometry Based Proteomics, Crystina Leah Kriss

Graduate Theses and Dissertations

Alcohol liver disease (ALD) is a major health concern throughout the world. Currently, in the United States, 17 million people suffer from alcoholism, of which 1.4 million people are receiving treatment [1, 2]. The link between ethanol metabolism, reactive oxygen species (ROS) and liver injury in ALD has been well characterized over the last couple decades [3-10]. Ethanol metabolism relies on the availability of the cofactor NAD+ for the oxidation of ethanol into acetate, consequently causing alterations in redox potential. Redox dysfunction within the mitochondria can affect multiple pathways important in maintaining cellular homeostasis. Chapter 1 provides an introduction ...


Gcn5 Impacts Fgf Signaling At Multiple Levels And Activates C-Myc Target Genes During Early Differentiation Of Embryoid Bodies, Li Wang Aug 2017

Gcn5 Impacts Fgf Signaling At Multiple Levels And Activates C-Myc Target Genes During Early Differentiation Of Embryoid Bodies, Li Wang

UT GSBS Dissertations and Theses (Open Access)

Precise control of gene expression during development is orchestrated by transcription factors, signaling pathways and co-regulators, with complex cross-regulatory events often occurring. Growing evidence has identified chromatin modifiers as important regulators for development as well, yet how particular chromatin modifying enzymes affect specific developmental processes remains largely unclear. Embryonic stem cells (ESCs) are self-renewing, pluripotent, and have the abilities to generate almost all cell types in adult tissues. The dual capacity of ESCs to self-renew and differentiate offers unlimited potential for studying gene regulation events at specific developmental stages in vitro that parallel developmental events during embryogenesis in vivo.

In ...


Regulation Of Alteration/Deficiency In Activation 3 (Ada3) By Acetylation And Its Role In Cell Cycle Regulation And Oncogenesis, Shashank Srivastava Dec 2016

Regulation Of Alteration/Deficiency In Activation 3 (Ada3) By Acetylation And Its Role In Cell Cycle Regulation And Oncogenesis, Shashank Srivastava

Theses & Dissertations

The ADA3 (Alteration/Deficiency in Activation 3) protein is a transcriptional adaptor protein that was initially discovered as a component of several HAT (Histone Acetyltransferase) complexes, the enzyme complex responsible for histone acetylation, which is a prerequisite for transcription. Earlier the studies from Dr. Band’s laboratory and that of others’ have deciphered a crucial role of ADA3 in cell cycle regulation (both through G1/S and G2/M phase transitions) and in maintaining the genomic stability.

While our laboratory investigated the mechanism behind the role of ADA3 in G1/S transition, the same remained unknown for ...


Tubulin Post-Translational Modifications Are Altered By Changes In Actin-Myosin Contractility In Non-Muscle Cells, James Mcgee Jun 2016

Tubulin Post-Translational Modifications Are Altered By Changes In Actin-Myosin Contractility In Non-Muscle Cells, James Mcgee

Honors Theses

All cells regulate their contractility by the interaction of actin and myosin. In non-muscle cells, however, this interaction is regulated by rho, a GTPase, which is the upstream effector for multiple pathways. Cell contractility increases when rho is active, and prior research has shown the depolymerization of microtubules (MTs) activates rho. Microtubules play a role in many cellular functions and it is thought that either associations with MT-associated proteins and/or post-translational modifications to tubulin regulate MT functions. Numerous post-translational modifications (PTMs) to microtubules have been identified, but their roles are not well understood. A possible relationship between changes in ...


Id4 Acts As A Tumor Suppressor Via P53: Mechanistic Insight, Derrick J. Morton Jr. May 2016

Id4 Acts As A Tumor Suppressor Via P53: Mechanistic Insight, Derrick J. Morton Jr.

Electronic Theses & Dissertations Collection for Atlanta University & Clark Atlanta University

Overexpression of tumor-derived mutant p53 is a common event in tumorigenesis, suggesting an advantageous selective pressure in cancer initiation and progression. Given that p53 is found to be mutated in 50% of all human cancers, restoration of mutant p53 to its wild type biological function has been a widely sought after avenue for cancer therapy. Most research efforts have largely focused on restoration of mutant p53 by artificial means given that p53 has some degree of conformational flexibility allowing for introduction of short peptides and artificial compounds. Recently, theoretical modeling and studies focused on restoration of mutant p53 by physiological ...


The Effect Of Posttranslational Modifications On Protein Aggregation, Morphology, And Toxicity, Mu Yang Jan 2016

The Effect Of Posttranslational Modifications On Protein Aggregation, Morphology, And Toxicity, Mu Yang

Dissertations, Master's Theses and Master's Reports

Proteins are one of the most versatile macromolecules in the biological system. The function or activity of a protein highly depends on its 3D native structure. However, under stress, they are at risk of misfolding/aggregation, leading to formation of structures that can indicate loss of function or gain of toxicity. In severe cases, protein aggregation can result in many diseases, including neurodegenerative diseases, such as Alzheimer’s, Parkinson’s, Huntington’s, and amyotrophic lateral sclerosis. Due to the heterogeneous nature of cellular environment and protein molecules, mechanism of in vivo folding and related toxicity still remains elusive. To have ...


Introducing Multiple Sites Of Acetylation To Histone H3 Via Nonsense Suppression, Isaac Young Jan 2016

Introducing Multiple Sites Of Acetylation To Histone H3 Via Nonsense Suppression, Isaac Young

Graduate Theses and Dissertations

A common post-translational modification (PTM) of proteins is lysine acetylation. This is an especially ubiquitous PTM in the histones of chromatin, and is important for helping to regulate both structural and mechanistic aspects of chromatin. The fundamental unit of chromatin is called the nucleosome and is made up of DNA that wraps around a histone protein octamer. Protruding from the nucleosome are 10 unstructured “tails” which protrude into the aqueous environment. A number of strategies exist for generating acetylated nucleosomes for the in-vitro study of chromatin including: Purification from eukaryotic organisms, chemical acetylation, amino acid analog incorporation, enzyme mediated acetylation ...


Post-Translational Control Of Retinoblastoma Protein Phosphorylation, Paul M. Stafford Sep 2014

Post-Translational Control Of Retinoblastoma Protein Phosphorylation, Paul M. Stafford

Electronic Thesis and Dissertation Repository

The retinoblastoma tumor suppressor protein (pRB) functions through multiple mechanisms to serve as a tumor suppressor. pRB has been well characterized to be inactivated through phosphorylation by CDKs. pRB dephosphorylation and activation is a much less characterized aspect of pRB function. In this thesis, I detail work to study the post translational control of pRB phosphorylation. Here I present work detailing efforts to generate a gene targeted mouse which disrupts PP1 binding to the C-terminus of pRB, allowing for detailed study of the mechanisms of pRB dephosphorylation. This work also details an examination of acetylation in the C-terminus of pRB ...


Characterization Of A Putative Sir2 Like Deacetylase And Its Role In Sabp2 Dependent Salicylic Acid Mediated Pathways In Plant, Md I. Haq Aug 2014

Characterization Of A Putative Sir2 Like Deacetylase And Its Role In Sabp2 Dependent Salicylic Acid Mediated Pathways In Plant, Md I. Haq

Electronic Theses and Dissertations

Salicylic Acid Binding Protein2 (SABP2) is an enzyme known to play important role in SA mediated pathway. SBIP-428 (SABP2 Interacting Protein-428), a SIR2 like deacetylase, has been found to interact with SABP2. We demonstrate that SBIP-428 functions as a Sirtuin deacetylase. We show that SBIP-428 itself is lysine acetylated. Interactions of a SBIP-428 with SABP2 also raised the possibility of SABP2 itself being lysine acetylated. The recombinant purified SABP2 or native partially purified SABP2 displayed no acetylation. In response to TMV infection, the expression of SBIP-428 was down regulated at 48 hpi. In addition, SBIP-428 was up regulated in plant ...


The Role Of Cyp33 In Mll Mediated Gene Repression, Steven D. Poppen Jan 2012

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 ...


Understanding The Role Of Histones During Chromosome Segregation: A Study Of The Effects Of Histone Gene Dosage In Saccharomyces Cerevisiae, Rebecca Leigh Danforth May 2009

Understanding The Role Of Histones During Chromosome Segregation: A Study Of The Effects Of Histone Gene Dosage In Saccharomyces Cerevisiae, Rebecca Leigh Danforth

Theses and Dissertations

Chromatin plays a role in all cellular functions that involve DNA. These include, but are not limited to replication, recombination, transcription, and chromosome segregation. Chromosome segregation is an extremely well conserved cellular process and is essential for maintaining the genetic integrity of a cell. There is very strong evidence indicating that chromatin structure is critical for maintaining the fidelity of chromosome transmission, but its specific role(s) in this process remains unclear. Chromatin is comprised of arrays of nucleosomes that serve to compact DNA. These nucleosomes consist of 146 bp of DNA that is wrapped around a histone octamer; two ...