Dissertation/Thesis Abstract

Study of human transcriptional factor dim2 and its interaction with splicing factor 1
by Guo, Feng, Ph.D., Illinois Institute of Technology, 2009, 92; 3370896
Abstract (Summary)

To understand pathogenesis of many diseases, it is very important to study the control of transcription since many diseases are caused by imbalances between positive and negative transcription controls. Expression of a particular gene may be controlled by a number of transcription factors. We identified the human splicing factor 1(SF1) as an interaction partner with the transcriptional factor dim2 in two-hybrid screen. To better understand the mechanisms underlying the interaction between dim2 and SF1, and the consequences of this interaction on the splicing progress and on the regulation of downstream gene expression, a series of experiments were carried out to investigate the protein-protein interaction between different domain(s) of SF1 and dim2, and between SF1 and dim2 mutations by mutagenesis assay and yeast two-hybrid tests. The C-terminal proline rich domain of SF1 is characterized to be the key component for binding with dim2 and the other domain(s) of SF1 protein may inhibit/affect the binding. On the other hand, four mutation sites located on two helices and two loop regions of dim2 are identified as essential for dim2-SF1 interaction. The high resolution dim2 structure determined at 1.33 Å by X-ray crystallography further provides structural basis for the functional study on this protein. Although the mechanism of the dim2 functions as splicing regulator remains to be investigated, these results indicate that dim2 interacts with SF1 directly, which may regulate gene expression through the early stage of pre-mRNA splicing.

Indexing (document details)
Advisor: Zhang, Yu-Zhu
Commitee:
School: Illinois Institute of Technology
School Location: United States -- Illinois
Source: DAI-B 70/08, Dissertation Abstracts International
Source Type: DISSERTATION
Subjects: Molecular biology, Cellular biology, Biophysics
Keywords: Dim2, Pre-mRNA splicing, Splicing factor 1, Structure, X-ray crystallography, Yeast two-hybrid
Publication Number: 3370896
ISBN: 9781109322897
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