Date of Award

2009

Degree Type

Thesis

Department

Biological, Geological and Environmental Sciences

First Advisor

Weyman, Crystal

Subject Headings

Myoblasts, Apoptosis, Cell differentiation, Ras oncogenes, Myf5, Skeletal myogenesis, Apoptosis, Differentiation, Oncogenic ras, Cancer

Abstract

Skeletal myogenesis is initiated by a family of muscle regulatory factors (MRFs) composed of the transcription factors MyoD, Myf5, MRF4, and myogenin. Of these, MyoD was the first discovered, is the most studied, and plays a well-characterized role in skeletal myoblast determination and differentiation. Our laboratory has also discovered that MyoD plays an important role in the apoptotic process that occurs in a subpopulation of myoblasts induced to differentiate. Expression of oncogenic Ras is known to inhibit myoblast differentiation and to decrease the expression of MyoD mRNA and protein. Our laboratory was the first to report that expression of oncogenic Ras also blocks the apoptotic process. While it is well known that MyoD and Myf5 function somewhat redundantly with respect to their role in the differentiation process, neither the role of Myf5 in the apoptotic process nor the regulation of Myf5 by oncogenic Ras has been investigated. Herein we report that, unlike MyoD, Myf5 is not sufficient to induce apoptosis. Further, like MyoD, Myf5 expression is decreased in both myoblasts and fibroblasts expressing oncogenic Ras. Additionally, we report that the mechanism of this inhibition is not a consequence of reducing Myf5 mRNA levels

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