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Articles 1 - 9 of 9

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

A Noncanonical Function Of The Telomerase Rna Component In Human Embryonic Stem Cells, Kirsten Ann Brenner Dec 2019

A Noncanonical Function Of The Telomerase Rna Component In Human Embryonic Stem Cells, Kirsten Ann Brenner

Arts & Sciences Electronic Theses and Dissertations

Telomeres are stretches of TTAGGG nucleotide repeats located at the ends of linear chromosomes that shorten with progressive cell division and prevent genomic instability at the cost of limiting a cell’s capacity to proliferate. This limitation can be overcome by telomerase, a ribonucleoprotein complex that elongates telomeres via reverse-transcription of the template telomerase RNA component (TERC). Recent studies have reported potential functions of TERC outside of its role in telomere maintenance. These noncanonical functions of TERC are however poorly defined, and the molecular mechanisms and biological relevance behind such functions remain elusive. Here, we generated conditional TERC knock-out human embryonic …


Exploration Of Ataxia Telangiectasia And Rad3-Related’S (Atr’S) Role In Cell Death Regulation: Implications In Development, Cancer, And Stroke, Brian Cartwright Dec 2019

Exploration Of Ataxia Telangiectasia And Rad3-Related’S (Atr’S) Role In Cell Death Regulation: Implications In Development, Cancer, And Stroke, Brian Cartwright

Electronic Theses and Dissertations

From gametogenesis until death an organism’s genome is under constant bombardment from endogenous and exogenous sources of DNA damage. To maintain genomic integrity amid this damage, cells have evolved responses which allow them to either preserve viability for recovery or initiate self-destructive pathways depending on the severity of DNA damage. One protein involved in initiating and carrying out these responses is the protein kinase ataxia telangiectasia and Rad3-related (ATR). ATR is known primarily for its regulatory role in initiating the checkpoint-signaling cascade following DNA damage and replicative stress. These signaling events lead to cell cycle arrest, DNA repair, or apoptosis …


High Molecular-Weight Hyaluronan Prevents Basal Cell Carcinoma Via Promoting Apoptosis In Cancer-Initiating Adult Stem Cells, Violet Liu Apr 2019

High Molecular-Weight Hyaluronan Prevents Basal Cell Carcinoma Via Promoting Apoptosis In Cancer-Initiating Adult Stem Cells, Violet Liu

Electronic Thesis and Dissertation Repository

Basal cell carcinoma (BCC), a keratinocyte cancer, is the most common human neoplasm worldwide. Although rarely metastatic, BCC is associated with high morbidity rates with globally rising incidence rates. Accompanying the increase in newly diagnosed cases, the societal cost for BCC treatment in Canada is also expected to inflate, exceeding over $900 million/year by 2031. Chronic UVB exposure has been identified as the primary carcinogen that causes activating mutations in the hedgehog signaling pathway. However, there are no effective preventative methods against BCC, since meta-analyses report sunscreen application does not reduce BCC in compliant patients. The native high molecular-weight hyaluronan …


Mechanisms Of Oriented Cell Division And Their Roles In Tissue Development, Evan Blake Dewey Apr 2019

Mechanisms Of Oriented Cell Division And Their Roles In Tissue Development, Evan Blake Dewey

Biology ETDs

Properly executed cell division is crucial to development, maintenance, and longevity of multicellular organisms. Defects in both symmetric and asymmetric divisions can lead to improper developmental patterning, as well as genomic instability, disruption of tissue homeostasis, and cancer. Our research focuses on how regulators orchestrate proper cell divisions. Mushroom Body Defect (Mud) is one such regulator, and here we describe how Mud is regulated via the Hippo signaling pathway kinase Warts (Wts), showing Wts phosphorylates Mud to enhance interaction with the polarity protein Partner of Inscuteable, promoting spindle orientation activity. We next focus on another regulator, Shortstop (Shot), describing a …


Evaluating The Therapeutic Potential Of Crocin Against Diethylnitrosamine Induced Experimental Hepatocellular Carcinoma In Rats, Basma Ali Mustafa Awad Apr 2019

Evaluating The Therapeutic Potential Of Crocin Against Diethylnitrosamine Induced Experimental Hepatocellular Carcinoma In Rats, Basma Ali Mustafa Awad

Theses

Hepatocellular carcinoma (HCC) is the fifth most common type of cancer and the third cause of cancer-related death worldwide. Liver cancer is the result of repeated injuries to the liver triggered by different causes. Currently, sorafenib is the only drug U.S. Food and Drug Administration approved targeted therapy. Sorafenib, an oral multikinase inhibitor, which inhibits the proliferation of tumor cells and blocks angiogenesis. Sorafenib has been shown to treat early and mild HCC lesions and it helped increase the survival rates at one year, but for only 44% of patients. Chemotherapies are an important line of defense when it comes …


Probing Apoptotic Caspase Allostery And Exosite Interactions For Alternative Regulation, Derek J. Macpherson Mar 2019

Probing Apoptotic Caspase Allostery And Exosite Interactions For Alternative Regulation, Derek J. Macpherson

Doctoral Dissertations

Programmed cell death, or apoptosis is a critical homeostatic pathway that monitors the balance of cell life and death. Apoptosis is regulated by a class of enzymes known as the cysteine aspartic proteases, or the caspases. The 12 human caspases that play important roles in the progression and regulation of apoptosis and inflammation. Caspases are tightly regulated by numerous factors including enzymatic activation, post-translational modifications, metal ligand binding, and protein modulation. Aberrant caspase activation and regulation has been implicated in the progression of numerous diseases such as proliferative diseases and neurodegeneration. The deeply entwined nature of caspases and apoptosis makes …


Autophagic Flux Modulation By Wnt/Β-Catenin Pathway Inhibition In Hepatocellular Carcinoma, Lilia Turcios, Heather E. Chacon, Catherine Garcia, Pedro Eman, Virgilius Cornea, Jieyun Jiang, Brett T. Spear, Chunming Liu, David S. Watt, Francesc Marti, Roberto Gedaly Feb 2019

Autophagic Flux Modulation By Wnt/Β-Catenin Pathway Inhibition In Hepatocellular Carcinoma, Lilia Turcios, Heather E. Chacon, Catherine Garcia, Pedro Eman, Virgilius Cornea, Jieyun Jiang, Brett T. Spear, Chunming Liu, David S. Watt, Francesc Marti, Roberto Gedaly

Surgery Faculty Publications

Autophagy targets cellular components for lysosomal-dependent degradation in which the products of degradation may be recycled for protein synthesis and utilized for energy production. Autophagy also plays a critical role in cell homeostasis and the regulation of many physiological and pathological processes and prompts this investigation of new agents to effect abnormal autophagy in hepatocellular carcinoma (HCC). 2,5-Dichloro-N-(2-methyl-4-nitrophenyl) benzenesulfonamide (FH535) is a synthetic inhibitor of the Wnt/β-catenin pathway that exhibits anti-proliferative and anti-angiogenic effects on different types of cancer cells. The combination of FH535 with sorafenib promotes a synergistic inhibition of HCC and liver cancer stem cell proliferation, …


A H2ax–Carp-1 Interaction Regulates Apoptosis Signaling Following Dna Damage, Sreeja C. Sekhar, Jaganathan Venkatesh, Vino T. Cheriyan, Magesh Muthu, Edi Levi, Hadeel Assad, Paul Meister, Vishnu V. Undyala, James W. Gauld, Arun K. Rishi Feb 2019

A H2ax–Carp-1 Interaction Regulates Apoptosis Signaling Following Dna Damage, Sreeja C. Sekhar, Jaganathan Venkatesh, Vino T. Cheriyan, Magesh Muthu, Edi Levi, Hadeel Assad, Paul Meister, Vishnu V. Undyala, James W. Gauld, Arun K. Rishi

Chemistry and Biochemistry Publications

Cell Cycle and Apoptosis Regulatory Protein (CARP-1/CCAR1) is a peri-nuclear phosphoprotein that regulates apoptosis via chemotherapeutic Adriamycin (doxorubicin) and a novel class of CARP-1 functional mimetic (CFM) compounds. Although Adriamycin causes DNA damage, data from Comet assays revealed that CFM-4.16 also induced DNA damage. Phosphorylation of histone 2AX (γH2AX) protein is involved in regulating DNA damage repair and apoptosis signaling. Adriamycin or CFM-4.16 treatments inhibited cell growth and caused elevated CARP-1 and γH2AX in human breast (HBC) and cervical cancer (HeLa) cells. In fact, a robust nuclear or peri-nuclear co-localization of CARP-1 and γH2AX occurred in cells undergoing apoptosis. Knock-down …


The Role Of The Cell-Surface Protease Tmprss13 In Colorectal Cancer, Fausto Alexander Varela Jan 2019

The Role Of The Cell-Surface Protease Tmprss13 In Colorectal Cancer, Fausto Alexander Varela

Wayne State University Dissertations

Colorectal cancer (CRC) is one of the most common and deadly cancers in both men and women in the United States. Extracellular proteolysis is often dysregulated in cancer including (CRC), resulting in degradation of extracellular matrix, as well as cleavage, processing, or shedding of cell adhesion molecules, growth factors, and cytokines. Several members of the type II transmembrane serine protease (TTSP) family have been shown to play critical roles in cancer progression; however, many family members have not yet been characterized in malignancy. We identified TMPRSS13 transcript to be upregulated in CRC compared to normal colon. This increase was confirmed …