Investigating SMAD involvement in Transforming Growth Factor-beta signal transduction: identification, characterization and transcriptional regulation of Gadd45beta

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Publication Type dissertation
School or College School of Medicine
Department Oncological Sciences
Author Major, Michael Benjamin
Title Investigating SMAD involvement in Transforming Growth Factor-beta signal transduction: identification, characterization and transcriptional regulation of Gadd45beta
Date 2004-05
Description Normal epithelial cells are in constant communication with their surrounding environment, largely through the detection, interpretation, and response to extracellular signaling molecules. The Transforming Growth Factor-beta (TGFbeta) supeifamily of growth factors comprises over 30 such signaling molecules in humans, many of which figure prominendy in development, tissue homeostasis and disease. Cells interpret the TGFbeta signal by integrating a multitude of signals into a cell type and context-dependent transcriptional profile. The transcripts comprising this profile are functionally responsible for the resulting phenotypic response, and consequently their identification and characterization is central to understanding TGFbeta in normal and diseased states. Therefore, we employed a global transcriptional profiling strategy to identify TGFbeta regulated genes in normal and cancerous tissues. This led to the cloning and characterization of Gadd45beta. We found that Gadd45beta transcriptional responsiveness to TGFbeta required the expression of the SMAD3 and SMAD4 transcription factors and the presence of a highly conserved 3-prime enhancer within the Gadd45p genomic locus. Using mammalian cell culture and zebrafish model systems, we discovered an essential role for Gadd45beta in the TGFbeta cytostatic program and metazoan development, respectively. Additionally, our expression screen led to the identification of the Kindlerin gene, a novel TGFbeta regulated gene involved in cell adhesion and spreading. In sum, our findings provide important advancements towards understanding how normal and transformed cells interpret and respond to members of the TGPbeta family of cell signaling molecules. work possible
Type Text
Publisher University of Utah
Subject Cellular Signal Transduction; Genetic Transcription
Subject MESH Transduction, Genetic; Signal Transduction; Gene Expression Regulation
Dissertation Institution University of Utah
Dissertation Name PhD
Language eng
Relation is Version of Digital reproduction of “Investigating SMAD involvement in Transforming Growth Factor-beta signal transduction: identification, characterization and transcriptional regulation of Gadd45beta.” Spencer S. Eccles Health Sciences Library. Print version of “Investigating SMAD involvement in Transforming Growth Factor-beta signal transduction: identification, characterization and transcriptional regulation of Gadd45beta.” available at J. Willard Marriott Library Special Collection. QP6.5 2004 .M35.
Rights Management © Michael Benjamin Major.
Format Medium application/pdf
Format Extent 8,149,452 bytes
Identifier undthes,4667
Source Original: University of Utah Spencer S. Eccles Health Sciences Library (no longer available).
Funding/Fellowship Huntsman Cancer Institute and the Pharmaceutical Research and Manufacturers of American (PhRMA) Foundation.
Master File Extent 8,149,523 bytes
ARK ark:/87278/s6np2684
ID 191817
setname ir_etd
Reference URL https://collections.lib.utah.edu/details?id=191817
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