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Understanding the mechanisms of transcriptional control by the oncoprotein MYC / by Mandeep Kaur.

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Author	Kaur, Mandeep.
Title	Understanding the mechanisms of transcriptional control by the oncoprotein MYC / by Mandeep Kaur.
Date	2013
Abstract	Even though 25 years have passed since the discovery of MYC, a complete understanding of the mechanism(s) of transcriptional control by this oncogenic transcription factor has not been achieved. Mcy is one of the most frequently deregulated oncogenes in a multitude of cancers and it is therefore imperative to develop a thorough understanding of its mechanistic actions. While Myc is essential for the proliferation of most cells, it has pleiotropic effects on cells: it induces cell growth, promotes apoptosis, affects G1-S cell cycle transitions and also induces cellular transformation. These simultaneous and complex biological effects of Myc have mire efforts to underline the single, most fundamental role of this oncogene. In terms of Myc's role as an activating transcription factor, work from several groups has clearly demonstrated the mechanism by which Myc transactivates target genes leading to a unified model of gene activation which comprises the recruitment of co-factors to target genes resulting in acetylation of neighboring histone tails ultimately leading to increased transcription. In addition, over the past few years, a new and exciting role for Myc as a factor that mediates RNA polymerase II transcriptional elongation has emerged but with little, if any, insight into a mechanism by which Myc performs this important function. While Myc mediated gene activation has been intensely studied over the years, the mechanism of Myc mediated represssion has not been given as much attention and has remained elusive despite the fact that Myc expression results in almost equal number of genes that are up and downregulated. Furthermore, one of the most important genes repressed by Myc is Myc itself in a negative feedback loop known as autoregulation. This phenomenon is particularly important in Myc's ability to induce tumorigenesis as small changes in the levels of Myc in a cell is sufficient to tip the balance towards malignant transformation. The work described herein provides evidence that supports a novel epigen
Description	xii, 234 leaves : ill. (some col.) 28 cm.
Format	application/pdf
Advisor	Michael D. Cole, Yolanda Sanchez, James DiRenzo, Lawrence Myers, Steven B. McMahon
College	Dartmouth Medical School.
Issuing Body	Dartmouth Dissertations are made available through the Dartmouth Digital Library.
Degree	Thesis (Ph.D.)--Dartmouth College.
Copyright	All rights reserved. No part of this book may be reproduced in any form by any electronic or mechanical means without permission in writing from the author.
DOI	http://dx.doi.org/10.1349/ddlp.976

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