Functional Study of the Hinge Region
of the Androgen Receptor
Acta Biomedica Lovaniensia, No. 415
By Tamzin Tanner
December 2007
Leuven University Press
Distributed By Coronet Books
ISBN: 9789058676597 
111 pages, Illustrated, 6 1/8 x 9 1/2"
$99.50 Paper Original
Abbreviations
Chapter 1:Introduction 1.1 The nuclear receptor family
1.2 Androgens
1.3 The androgen receptor (AR)
1.3.1 The AR gene
1.3.2 The modular structure of the AR protein
1.3.3 The AR gene
1.3.4 Regulation of cellular localization of the AR
1.3.5 Post-translational modifications of the AR protein
1.3.6 AR degradation
1.3.7 The role of the proteasome in AR transcriptional regulation
1.3.8 Intranuclear mobility and distribution of the AR
1.3.9 Diseases associated with AR dysfunction
1.4 Regulation of gene transcription
1.4.1 Chromatic structure and histone modifications
1.4.2 ATP-dependent chromatin remodelling
1.4.3 Histone modifications
1.4.4 Mediator, RNA-polymerase II and transcription initiation
1.5 Aim and scope of the study
Chapter 2:Materials and methods 2.1 Materials
2.2 Plasmid constructs
2.2.1 Reporter constructs
2.2.2 Flag-tagged AR expression constructs
2.2.3 Flag-tagged Gal4-DBD fusion protein expression constructs
2.2.4 EGFP-tagged AR expression constructs
2.3 Mammalian cell structure
2.4 Transient transfections, luciferase and beta-galactosidase assays
2.5 Western blotting
2.6 Immunocytochemistry and fluorescence microscopy
2.7 Electrophoretic-mobility shift assays (EMSAs)
2.8 Hep3B stable cell-lines
2.9 Fluorescent recovery after photo-bleaching (FRAP) analysis
2.10 Computational analysis of FRAP data
Chapter 3: Defining the roles of the inhibitory region in androgen receptor function 3.1 Defining the inhibitory region and the inhibitory motif
3.2 The inhibitory region regulates the nuclear translocation and DNA binding potential of the androgen receptor
3.3 The role of the inhibitory region on proteasome-mediated events in androgen receptor action
3.4 The influence of the hinge region on the constitutively active activation function 1 (AF-1)
3.5 An investigation of the inhibitory motif as a potential degron
3.6 Discussion
Chapter 4: The hinge region is a multi-functional domain that regulates the intranuclear mobility of the androgen receptor 4.1 Identification of the functional residues in the inhibitory region
4.2 The putative helical structure of the hinge region
4.3 The positively-charged residues in the hinge region have multiple functions
4.4 The charged residues of the hinge region play a role in DNA-binding
4.5 A decreased DNA binding affinity results in an increased activation potential
4.6 The inhibitory region regulates the intranuclear mobility of the androgen receptor
4.7 Computational analysis of fitted FRAP data
4.8 Discussion
Chapter 5: General conclusions and future perspectives 5.1 General conclusions
5.2 future perspectives
5.2.1 The positively-charged residues in the hinge region have multiple functions
5.2.1 The positively-charged residues in the hinge region have multiple functions
5.2.2 The positively-charged residues in the hinge region have multiple functions
5.2.3 The positively-charged residues in the hinge region have multiple functions
5.2.4 The positively-charged residues in the hinge region have multiple functions
5.2.5 The positively-charged residues in the hinge region have multiple functions
5.2.6 The positively-charged residues in the hinge region have multiple functions
Summary / Samenvatting
References
Medical Science; Genetics