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Identifier uch.med.msc//2004nikolaidou
Title Ο ρόλος των πυρηνικών υποδοχέων ορμονών και της πρόλινο ισομεράσης Pin 1 στη ρύθμιση των γονιδίων των απολιποπρωτεϊνών του ανθρώπου
Creator Nikolaidou-Neokosmidou, Varvara
Abstract Διατμηματικό, συνεργαζόμενα Τμήματα Βιολογίας και Ιατρικής του Πανεπιστημίου Κρήτης. The focus of the present work is the role of hormone nuclear receptors in the transcriptional regulation of the genes coding for apolipoprotein A-I and C-III. ApoA-I is the main protein component of high density lipoproteins (HDL) and plays an important protective role against the development of atgherosclerosis whereas apoC-III is involved in the catabolism of triglyceride-rich lipoprotein particles. In the first part of the present work we studied in vivo the recruitement of the orphan huclear receptor Hepatocyte Nuclear Factor 4 (HNF-4) to the promoters and the common enhancer of the apoA-I and apoC-III genes using chromatin immunoprecipitations. In the second part, we investigated the possible prole of prolyl isomerase Pin1 in the transcriptional activity of the hormone huclear receptors HNF-4 and RXR (Retinoid X Receptor). We also studied the involvement of Pin1 in the transcriptional regulation of various apolipoprotein promoters. Finally, in the third part of the present work, we took advantage of a recently described sensitive system for protein-protein interactions which is based on protein biotinylation in vivo in order to study the physical interactions between hormone nuclear receptors and various regulatory factors such as the isomerase Pin, the Transforming Growth Factor β regulated Smad proteins as well as members of the AP1 family of transcription factors (c-jun, junB, junD, ATF-2). For this purpose we constructed hybrid proteins of HNF-4 and RXRα bearing a short 22 amino acid peptide tag at their N-terminus. This peptide is recognized and biotinylated at a specific lysine residue by the bacterial protein ligase BirA in vivo. The ultimate goal of this work is to understand in depth the mechanisms by which the apolipoprotein genes are regulated. This knowledge may lead in the future to the development of novel drugs for the treatment of hyperilipidemias in humans. Understanding the role of Pin1 on the activity of nuclear receptors may also have wider implications for the treatment of diseases that are caused by the deregulation of this important class of transcitpion factors such as cancer.
Issue date 2004-12-01
Date available 0000-00-01
Collection   School/Department--School of Medicine--Department of Medicine--Post-graduate theses
  Type of Work--Post-graduate theses
Permanent Link https://elocus.lib.uoc.gr//dlib/e/0/2/metadata-dlib-2004nikolaidou.tkl Bookmark and Share
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