Tavtigian, Sean Vahram (1992) The regulatory capacity of the protooncogene c-myc. Dissertation (Ph.D.), California Institute of Technology. http://resolver.caltech.edu/CaltechTHESIS:09142011-101754107
Myc is a crucial regulatory gene capable of altering normal cellular proliferation and differentiation. Its mechanism of action is largely unknown. The cloning and identification of downstream myc regulatory targets constitutes a key step towards deeper understanding.
Beginning with a conditional c-myc expression system and a physiologic setting where conditional myc expression produced clear phenotypic effects at both cell cycle progression and mRNA expression levels, I cloned a set of myc regulated genes. The frequency with which myc targets were identified "among a panel of cDNAs subject to either up or downregulation during G_l of the first cell cycle following serum stimulated emergence from growth arrest suggested that only about one-third of such genes may be myc targets. Consequently, this work has extended the myc target gene class to include several extracellular matrix proteins, one anabolic and one catabolic enzyme, a differentiation marker, several important cell proliferation regulators, and an assortment of unidentified genes.
While that cloning effort was in progress, two groups identified max, a gene encoding multiple bHLHzip proteins that can form DNA binding oligomers either alone or in a heterotypic complex with myc. After incorporating conditional max expression into the experimental paradigm of conditional myc expression, reexamination of the myc target gene set identified individual members that are cooperatively upregulated by myc and max and members that are regulated in opposite directions by myc and by max. In addition, we made the entirely unexpected observation that max is a regulator of a specific subset of the immediate early serum response gene class.
Based on the results of these studies, I propose an integrative model accounting for the diverse effects of myc and max on cellular function.
|Item Type:||Thesis (Dissertation (Ph.D.))|
|Subject Keywords:||Biochemistry.Molecular Biology|
|Degree Grantor:||California Institute of Technology|
|Major Option:||Biochemistry and Molecular Biophysics|
|Thesis Availability:||Restricted to Caltech community only|
|Defense Date:||21 May 1992|
|Default Usage Policy:||No commercial reproduction, distribution, display or performance rights in this work are provided.|
|Deposited By:||Dan Anguka|
|Deposited On:||15 Sep 2011 17:49|
|Last Modified:||26 Dec 2012 04:38|
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