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You searched for +publisher:"Vanderbilt University" +contributor:("Dr. Stephen Hann"). Showing records 1 – 2 of 2 total matches.

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Vanderbilt University

1. McCann, Tyler Scott. Elucidation of the Biological Function of the RPC Family Ubiquitin Ligase Asr1.

Degree: PhD, Cell and Developmental Biology, 2016, Vanderbilt University

Proper regulation of gene transcription is an essential process for any cell. Failure to precisely control the procedure of transcription can lead to developmental defects, disease, and even death. Within the last 20 years, ubiquitin, and other factors of the ubiquitin proteasome system have been shown to be extensively involved in the control of various steps of transcription. The Saccharomyces cerevisiae protein Asr1, is the defining member of an evolutionarily conserved set of proteins that contain a RING finger, a PHD finger, and a domain that binds the C-terminal repeat region of RNA polymerase II (RNAPII) called the RPC protein family. Asr1 is recruited to RNAPII in response to hyperphosphorylation of its regulatory C-terminal tail. Once bound, Asr1 oligoubiquitylates at least two subunits of RNAPII, leading to the ejection of the dissociable heterodimer Rpb4 and Rpb7, as well as the transcriptional inactivation of the polymerase complex. Despite the clear biochemical effects Asr1 has on RNAPII, a biological role for Asr1 within the cell has remained elusive. Within this dissertation, I present evidence that Asr1 is involved in the silencing of transcription of genes located at subtelomeric regions. Asr1 has been observed to associate with subtelomeric chromatin, and disruption of the ability of Asr1 to ubiquitylate RNAPII induces transcription at these regions. Asr1 also physically associates with Ubp3, a ubiquitin specific protease with a known role in the regulation of silent chromatin at sub-telomeric regions. I show that Asr1 and Ubp3 have antagonistic roles in both the ubiquitylation of RNAPII as well as the transcription of genes located in telomere proximal regions. The evidence presented in this dissertation reveal the importance of non-proteolytic ubiquitylation in the control of transcription, but also sheds light on a poorly understood family of eukaryotic ubiquitin-ligases. Advisors/Committee Members: Dr. Todd Graham (committee member), Dr. Melanie Ohi (committee member), Dr. Tony Weil (committee member), Dr. Stephen Hann (Committee Chair).

Subjects/Keywords: ubiquitin; silencing; RNA polymerase II; transcription; chromatin

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APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6th Edition):

McCann, T. S. (2016). Elucidation of the Biological Function of the RPC Family Ubiquitin Ligase Asr1. (Doctoral Dissertation). Vanderbilt University. Retrieved from http://hdl.handle.net/1803/10415

Chicago Manual of Style (16th Edition):

McCann, Tyler Scott. “Elucidation of the Biological Function of the RPC Family Ubiquitin Ligase Asr1.” 2016. Doctoral Dissertation, Vanderbilt University. Accessed September 28, 2020. http://hdl.handle.net/1803/10415.

MLA Handbook (7th Edition):

McCann, Tyler Scott. “Elucidation of the Biological Function of the RPC Family Ubiquitin Ligase Asr1.” 2016. Web. 28 Sep 2020.

Vancouver:

McCann TS. Elucidation of the Biological Function of the RPC Family Ubiquitin Ligase Asr1. [Internet] [Doctoral dissertation]. Vanderbilt University; 2016. [cited 2020 Sep 28]. Available from: http://hdl.handle.net/1803/10415.

Council of Science Editors:

McCann TS. Elucidation of the Biological Function of the RPC Family Ubiquitin Ligase Asr1. [Doctoral Dissertation]. Vanderbilt University; 2016. Available from: http://hdl.handle.net/1803/10415


Vanderbilt University

2. Kim, Jongchan. Modeling human prostate cancer development using transgenic mice with heterogeneous mutations.

Degree: PhD, Pathology, 2009, Vanderbilt University

Prostate cancer is the most commonly diagnosed cancer in American men. Although much progress has been made in identifying the genetic alterations that underlie this disease, there remains a gap in our understanding of how these genetic changes interact to lead to cancer. Modeling human cancers in vivo using mice is a critical part of cancer biology to better understand human carcinogenesis. Most human cancers are thought to initiate from a mutation in a single cell or a few cells, which expand and become cancerous with the accumulation of additional mutations. However, current mouse prostate cancer models do not accurately mimic this process as mutations are generally induced in entire cell populations rather than in a few cells. To more accurately model human prostate cancer, we generated novel transgenic mice with focal overexpression of the oncogene c-MYC in the prostatic epithelium. Focal c-MYC activation resulted in mild pathology despite expansion of the c-MYC-positive cells. When combined with heterozygous or homozygous deletion of the Pten tumor suppressor gene, however, focal c-MYC expression promoted the development of prostate cancer. Cells with concurrent activation of c-MYC and loss of Pten were of higher grade and out-proliferated cells with mutations in Pten alone. In the prostate, Pten deletion activates the p53 pathway, which can induce either apoptosis or senescence. We found that concurrent c-MYC expression shifted the p53 pathway response from senescence in favor of apoptosis. Thus cooperativity between c-MYC and Pten leads to increased tumorigenicity due to the high rates of proliferation and reduced senescence in c-MYC/Pten mutant cells in spite of elevated rates of apoptosis. Our model of focal c-MYC expression allowed us to examine the characteristics of cells with distinct mutations (c-MYC vs. wild type or Pten-null vs. c-MYC;Pten-null cells) in the same mouse prostate to gain insight into the interaction and competition between cells in the cancer progression. This system provides an important cancer model to investigate heterogeneous and incremental nature of human prostate carcinogenesis. Advisors/Committee Members: Dr. Stephen Hann (committee member), Dr. Gregory Sephel (committee member), Dr. Harold Moses (committee member), Dr. Neil Bhowmick (committee member), Dr. Richard Hoover (Committee Chair).

Subjects/Keywords: Transgenic mice; c-MYC; Prostate  – Cancer  – Animal models; Transgenic; Prostate cancer; Myc oncogenes

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APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6th Edition):

Kim, J. (2009). Modeling human prostate cancer development using transgenic mice with heterogeneous mutations. (Doctoral Dissertation). Vanderbilt University. Retrieved from http://hdl.handle.net/1803/14112

Chicago Manual of Style (16th Edition):

Kim, Jongchan. “Modeling human prostate cancer development using transgenic mice with heterogeneous mutations.” 2009. Doctoral Dissertation, Vanderbilt University. Accessed September 28, 2020. http://hdl.handle.net/1803/14112.

MLA Handbook (7th Edition):

Kim, Jongchan. “Modeling human prostate cancer development using transgenic mice with heterogeneous mutations.” 2009. Web. 28 Sep 2020.

Vancouver:

Kim J. Modeling human prostate cancer development using transgenic mice with heterogeneous mutations. [Internet] [Doctoral dissertation]. Vanderbilt University; 2009. [cited 2020 Sep 28]. Available from: http://hdl.handle.net/1803/14112.

Council of Science Editors:

Kim J. Modeling human prostate cancer development using transgenic mice with heterogeneous mutations. [Doctoral Dissertation]. Vanderbilt University; 2009. Available from: http://hdl.handle.net/1803/14112

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