Characterization of RNF43, a novel negative regulator of the Wnt signaling pathway:
Gespeichert in:
| 1. Verfasser: | |
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| Format: | Abschlussarbeit Buch |
| Sprache: | English |
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2013
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| Schlagworte: | |
| Online-Zugang: | Volltext https://nbn-resolving.org/urn:nbn:de:bvb:91-diss-20130411-1115453-0-4 Inhaltsverzeichnis |
| Beschreibung: | Zsfassung in dt. Sprache |
| Beschreibung: | XVIII, 234 S. Ill., graph. Darst. |
Internformat
MARC
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| 100 | 1 | |a Loregger, Anke |e Verfasser |4 aut | |
| 245 | 1 | 0 | |a Characterization of RNF43, a novel negative regulator of the Wnt signaling pathway |c Anke Loregger |
| 264 | 1 | |c 2013 | |
| 300 | |a XVIII, 234 S. |b Ill., graph. Darst. | ||
| 336 | |b txt |2 rdacontent | ||
| 337 | |b n |2 rdamedia | ||
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| 502 | |a München, Techn. Univ., Diss., 2013 | ||
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| 856 | 4 | 1 | |u http://mediatum.ub.tum.de/node?id=1115453 |x Verlag |z kostenfrei |3 Volltext |
| 856 | 4 | |u https://nbn-resolving.org/urn:nbn:de:bvb:91-diss-20130411-1115453-0-4 |x Resolving-System | |
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| 912 | |a ebook | ||
| 999 | |a oai:aleph.bib-bvb.de:BVB01-026018723 | ||
Datensatz im Suchindex
| _version_ | 1804150402390687744 |
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| adam_text | IMAGE 1
INDEX OF CONTENTS
INDEX O F CONTENTS ILL
INDEX OF FIGURES VIII
ABBREVIATIONS XI
SUMMARY XV
ZUSAMMENFASSUNG XVII
1 INTRODUCTION 1
1.1 INTESTINAL DEVELOPMENT 1
1.2 ARCHITECTURE, FUNCTION AND HOMEOSTASIS O F THE INTESTINE 2
1.3 INTESTINAL STEM CELLS 4
1.3.1 STEM CELL PROPERTIES 4
1.3.2 DIFFERENT MODELS O F INTESTINAL STEM CELLS 5
1.3.3 LOCALIZATION AND MAINTENANCE O F INTESTINAL STEM CELLS 8
1.4 COLON CANCER 9
1.4.1 EPIDEMIOLOGY O F COLON CANCER 9
1.4.2 HEREDITARY COLON CANCER 10
1.4.3 SPORADIC COLON CANCER 11
1.5 WNT SIGNALING PATHWAY 13
1.5.1 THE NON-CANONICAL WNT SIGNALING PATHWAYS 14
1.5.2 THE CANONICAL 13-CATENIN DEPENDENT WNT SIGNALING PATHWAY 17
1.5.3 WNT TARGET GENES 21
1.5.4 INHIBITORS O F THE WNT SIGNALING PATHWAY 21
1.5.5 THE ROLE O F WNT SIGNALING IN CANCER DEVELOPMENT 23
1.6 UBIQUITINATION 24
1.7 RING FINGER PROTEINS AND UBIQUITINATION 26
1.7.1 STRUCTURE O F RING FINGER PROTEINS 26
III
HTTP://D-NB.INFO/103711888X
IMAGE 2
1.7.2 FUNCTION O F RING FINGER PROTEINS 27
1.8 RING FINGER PROTEIN 43 28
1.9 PREVIOUS WORK ON RNF43 30
1.10 OBJECTIVES 33
2 MATERIALS AND METHODS 34
2.1 MATERIALS 34
2.1.1 CONSUMABLES 34
2.1.2 CHEMICALS AND REAGENTS 35
2.1.3 BUFFERS, MEDIA AND SOLUTIONS 38
2.1.4 BACTERIAL STRAINS 45
2.1.5 CELL LINES 45
2.1.6 ANTIBODIES 46
2.1.7 RESTRICTION ENZYMES 48
2.1.8 VECTORS 48
2.1.9 PRIMERS 50
2.1.10 INSTRUMENTS 54
2.1.11 SOFTWARE 56
2.2 METHODS 58
2.2.1 MICROBIOLOGICAL METHODS 58
2.2.2 MOLECULAR BIOLOGICAL METHODS 59
2.2.3 CELL CULTURE METHODS 61
2.2.4 PROTEIN BIOCHEMICAL METHODS 65
2.2.5 TOP/FOP LUCIFERASE REPORTER ASSAY 69
2.2.6 MRNA EXTRACTION, DNASEL TREATMENT AND CDNA PREPARATION 70
2.2.7 REAL-TIME PCR 71
2.2.8 WHOLE MOUNT IN SITU HYBRIDIZATION 73
2.2.9 PROLIFERATION ASSAYS 74
IV
IMAGE 3
2.2.10 IMMUNOFLUORESCENCE STAININGS 75
2.2.11 ANALYSES O F RNF43 GENE SEQUENCES 76
2.2.12 COLONY FORMATION ASSAYS 77
2.2.13 XENOPUS LAEVIS AXIS DUPLICATION ASSAYS 78
2.2.14 STATISTICAL ANALYSIS 78
3 RESULTS 79
3.1 EXPRESSION O F RNF43 82
3.1.1 EXPRESSION O F RNF43 IN MICE 82
3.1.2 EXPRESSION O F RNF43 IN HUMAN COLON CANCER SAMPLES AND CELL LINES
84
3.1.3 MODEL FOR INVESTIGATION O F EFFECTS ON WNT SIGNALING ACTIVITY 89
3.2 RNF43 IS A NEGATIVE REGULATOR O F FI-CATENIN/TCF4-MEDIATED
TRANSCRIPTIONAL ACTIVATION 92
3.2.1 THE RING DOMAIN O F RNF43 IS REQUIRED FOR INHIBITION O F
WNT/B-CATENIN SIGNALING 94
3.2.2 RNF43 INHIBITS WNT SIGNALING IN VIVO 95
3.2.3 RNF43 ACTS AT THE LEVEL OR DOWNSTREAM O F 0-CATENIN 97
3.3 FUNCTION O F RNF43 102
3.3.1 SUBCELLULAR LOCALIZATION O F RNF43 102
3.3.2 RECENTLY DESCRIBED FUNCTION O F RNF43 111
3.3.3 INTERACTION O F RN F43 AND PSF 115
3.3.4 INTERACTION O F RNF43 AND TCF4 119
3.3.5 INTERACTION O F RNF43 AND CTBP 123
3.3.6 EFFECT O F WILDTYPE AND MUTANT RNF43 ON TCF4 AND CTBP PROTEINS 124
3.3.7 AUTOUBIQUITINATION ACTIVITY O F RNF43 128
3.3.8 THE INHIBITORY EFFECT O F RNF43 ON WNT SIGNALING ACTIVITY IS
REVERSED BY MG132 130
3.3.9 EFFECT O F RNF43 ON PROLIFERATION AND CELL GROWTH 131
3.4 ANALYSIS O F RNF43 DELETION MUTANTS 139
3.4.1 N-TERMINAL DELETION MUTANTS 143
3.4.2 ROLE O F THE SIGNAL PEPTIDE 154
V
IMAGE 4
3.4.3 RNF43 MUTANTS LACKING THE TRANSMEMBRANE DOMAIN (AAAL 91 -228) 163
3.5 CLINICAL RELEVANCE 169
3.5.1 TRANSCRIPTIONAL REPRESSION O F RNF43 BY CPG METHYLATION IN COLON
CANCER CELL LINES 169
3.5.2 HIGH RNF43 MRNA EXPRESSION IS CORRELATED WITH POOR PROGNOSIS O F
TUMOR PATIENTS 171
3.5.3 RNF43 IS MUTATED IN TUMORS 175
3.6 RNF43 MICE 187
3.7 PROSPECTIVE 191
3.7.1 FUNCTION O F RNF43 IN CELL DIVISION 191
3.7.2 INVESTIGATION O F THE ROLE O F RNF43 IN INTESTINAL STEM CELLS 194
DISCUSSION 197
4.1 EXPRESSION O F RNF43 IN MICE AND HUMANS 197
4.1.1 CORRELATION O F RNF43 EXPRESSION AND ENDOGENOUS WNT SIGNALING
ACTIVITY 199
4.2 ROLE O F RNF43 IN THE WNT SIGNALING PATHWAY 200
4.2.1 SUBCELLULAR LOCALIZATION O F RNF43 202
4.2.2 RNF43 IS A HOMOLOGUE O F ZNRF3 203
4.2.3 INTERACTION PARTNERS O F RNF43 204
4.3 FUNCTION O F RNF43 AS AN UBIQUITIN E3-LIGASE 207
4.4 EFFECT O F KNOCKDOWN O F THE RNF43 GENE ON CELL GROWTH AND WNT
SIGNALING ACTIVITY 209
4.5 EFFECT O F ECTOPIC EXPRESSION O F RNF43 ON PROLIFERATION RATES AND
CELL GROWTH 210
4.6 FUNCTION O F TRUNCATED VERSIONS O F RNF43 211
4.7 ROLE O F RNF43 IN TUMORS 214
4.8 RNF43 KNOCKOUT MICE 217
4.9 THE LOCALIZATION O F ENDOGENOUS RNF43 PROTEIN 218
4.10 ANOTHER MECHANISM O F RNF43 FUNCTION 219
4.11 FUTURE PERSPECTIVES 220
4.11.1 INVESTIGATION O F THE ROLE O F RNF43 IN INTESTINAL STEM CELLS 220
4.11.2 INVESTIGATION O F THE ROLE O F RNF43 IN CELL CYCLE AND CELL
DIVISION 221
VI
IMAGE 5
4.11.3 ROLE O F RNF43 IN A COMPLEX NETWORK O F SIGNALING PATHWAYS 221
4.12 CLOSING REMARKS 221
5 REFERENCES 223
VII
|
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| spelling | Loregger, Anke Verfasser aut Characterization of RNF43, a novel negative regulator of the Wnt signaling pathway Anke Loregger 2013 XVIII, 234 S. Ill., graph. Darst. txt rdacontent n rdamedia nc rdacarrier Zsfassung in dt. Sprache München, Techn. Univ., Diss., 2013 (DE-588)4113937-9 Hochschulschrift gnd-content Erscheint auch als Online-Ausgabe urn:nbn:de:bvb:91-diss-20130411-1115453-0-4 http://mediatum.ub.tum.de/node?id=1115453 Verlag kostenfrei Volltext https://nbn-resolving.org/urn:nbn:de:bvb:91-diss-20130411-1115453-0-4 Resolving-System DNB Datenaustausch application/pdf http://bvbr.bib-bvb.de:8991/F?func=service&doc_library=BVB01&local_base=BVB01&doc_number=026018723&sequence=000001&line_number=0001&func_code=DB_RECORDS&service_type=MEDIA Inhaltsverzeichnis |
| spellingShingle | Loregger, Anke Characterization of RNF43, a novel negative regulator of the Wnt signaling pathway |
| subject_GND | (DE-588)4113937-9 |
| title | Characterization of RNF43, a novel negative regulator of the Wnt signaling pathway |
| title_auth | Characterization of RNF43, a novel negative regulator of the Wnt signaling pathway |
| title_exact_search | Characterization of RNF43, a novel negative regulator of the Wnt signaling pathway |
| title_full | Characterization of RNF43, a novel negative regulator of the Wnt signaling pathway Anke Loregger |
| title_fullStr | Characterization of RNF43, a novel negative regulator of the Wnt signaling pathway Anke Loregger |
| title_full_unstemmed | Characterization of RNF43, a novel negative regulator of the Wnt signaling pathway Anke Loregger |
| title_short | Characterization of RNF43, a novel negative regulator of the Wnt signaling pathway |
| title_sort | characterization of rnf43 a novel negative regulator of the wnt signaling pathway |
| topic_facet | Hochschulschrift |
| url | http://mediatum.ub.tum.de/node?id=1115453 https://nbn-resolving.org/urn:nbn:de:bvb:91-diss-20130411-1115453-0-4 http://bvbr.bib-bvb.de:8991/F?func=service&doc_library=BVB01&local_base=BVB01&doc_number=026018723&sequence=000001&line_number=0001&func_code=DB_RECORDS&service_type=MEDIA |
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