Tam Ka-ying. / Thesis (M.Phil.)--Chinese University of Hong Kong, 2006. / Includes bibliographical references (leaves 164-179). / Abstracts in English and Chinese. / Chapter Chapter one: --- Introduction --- p.4 / Chapter 1.1 --- Introduction of BRE --- p.4 / Chapter 1.1.1 --- Discovery of BRE --- p.4 / Chapter 1.1.2 --- cDNA sequence and amino acids sequence of BRE --- p.4 / Chapter 1.1.3 --- BRE expression level in Human and rat organs --- p.5 / Chapter 1.1.4 --- Expression of Human and mouse BRE in multiple isoforms --- p.6 / Chapter 1.1.4.1 --- BRE isoforms in Human --- p.6 / Chapter 1.1.4.2 --- BRE isoforms in mouse --- p.6 / Chapter 1.1.5 --- mRNA level of BRE upon stress --- p.7 / Chapter 1.1.6 --- BRE and steroidogenesis --- p.8 / Chapter 1.1.7 --- BRE and p55 tumor necrosis factor α (TNF) receptor --- p.9 / Chapter 1.1.8 --- BRE and NFkB activity --- p.9 / Chapter 1.1.9 --- Anti-apoptotic effect of BRE --- p.10 / Chapter 1.1.10 --- BRE enhances the growth of tumor cells --- p.12 / Chapter 1.1.11 --- BRE and its ubiquitination activity --- p.12 / Chapter 1.1.12 --- Regulation of Prohibitin and p53 expression and proliferation by BRE --- p.13 / Chapter 1.2 --- Regulation of transcription --- p.15 / Chapter 1.2.1 --- Cis-acting elements --- p.17 / Chapter 1.2.1.1 --- The TATA box --- p.18 / Chapter 1.2.1.2 --- The GC box and CAAT box --- p.18 / Chapter 1.2.1.3 --- The initiator (Inr) --- p.19 / Chapter 1.2.1.4 --- CpG islands --- p.20 / Chapter 1.2.2 --- Trans- acting protein factors --- p.21 / Chapter 1.2.2.1 --- Zinc finger domain --- p.21 / Chapter 1.2.2.2 --- Basic helix-turn-helix domain (bHLH) --- p.22 / Chapter 1.3 --- Hypothesis and Objectives --- p.23 / Chapter Chapter two: --- Materials and Methods --- p.25 / Chapter 2.1 --- Materials --- p.25 / Chapter 2.1.1 --- Primers used in polymerase chain reaction (PCR) and sequencing --- p.25 / Chapter 2.1.2 --- DNA clones used in the studies --- p.26 / Chapter 2.1.3 --- Materials for DNA manipulation --- p.27 / Chapter 2.1.4 --- Materials for protein manipulation --- p.28 / Chapter 2.1.5 --- Antibodies --- p.28 / Chapter 2.1.6 --- Chemical used in treatments --- p.29 / Chapter 2.1.7 --- Kits --- p.29 / Chapter 2.1.8 --- Culture media and reagents --- p.30 / Chapter 2.1.9 --- Instrumentation --- p.30 / Chapter 2.1.10 --- Bacterial strain used for transfection and cloning --- p.31 / Chapter 2.2 --- Methodologies --- p.36 / Chapter 2.2.1 --- Cell culture --- p.36 / Chapter 2.2.1.1 --- Monolayer cells --- p.36 / Chapter 2.2.1.2 --- Suspension cell --- p.36 / Chapter 2.2.2 --- Identification of the transcriptional start site (TSS) of BRE by RNA ligase- mediated rapid amplification of 5，and 3，cDNA ends (RLM-RACE) --- p.37 / Chapter 2.2.3 --- Preparation of the 5' untranslated region (UTR) fragments of BRE --- p.39 / Chapter 2.2.3.1 --- Polymerase chain reaction (PCR) with Taq polymerase --- p.39 / Chapter 2.2.3.2 --- Polymerase chain reaction (PCR) with PhusiońёØ high-fidelity DNA.… --- p.40 / Chapter 2.2.4 --- Construction of the reporter constructs --- p.42 / Chapter 2.2.5 --- Cell transfection --- p.42 / Chapter 2.2.6 --- Dual-luciferase reporter assay --- p.43 / Chapter 2.2.7 --- Western blotting --- p.44 / Chapter 2.2.8 --- Cell cycle analysis by flow cytometry --- p.45 / Chapter 2.2.9 --- BRE antibody production --- p.43 / Chapter Chapter Three: --- Identification of transcriptional start sites and promoter region for BRE --- p.52 / Chapter 3.1 --- Identification of the transcriptional start sites for BRE --- p.52 / Chapter 3.2 --- Computational analysis of the 5' region of BRE --- p.57 / Chapter 3.2.1 --- Putative transcriptional factor binding sites --- p.57 / Chapter 3.2.2 --- CpG island --- p.58 / Chapter 3.3 --- Identification of BRE promoter --- p.64 / Chapter Chapter Four: --- Characterization of transcriptional regulation of BRE --- p.70 / Chapter 4.1 --- Regulation of BRE promoter by genotoxic stimuli and retinoic acid --- p.71 / Chapter 4.1.1 --- Etoposide --- p.71 / Chapter 4.1.2 --- 4-nitroquinoline-l -oxide (4NQO) --- p.79 / Chapter 4.1.3 --- Retinoic acid (RA) --- p.87 / Chapter 4.2 --- Regulation of BRE promoter by p53 protein and gamma irradiation --- p.90 / Chapter 4.2.1 --- Co-transfection with p53 plasmid --- p.90 / Chapter 4.2.2 --- Gamma irradiation (y irradiation) --- p.96 / Chapter 4.2.2.1 --- γ irradiation treatment of HeLa cells --- p.96 / Chapter 4.2.2.2 --- γ irradiation treatment of Balb/c 3T3 cells --- p.99 / Chapter 4.3 --- Regulation of BRE promoter by BRE --- p.103 / Chapter 4.3.1 --- Co-transfection with V5-tagged BRE (GS-BRE) --- p.103 / Chapter 4.3 2 --- Co-transfection with untagged BRE (pcDNA3-BRE) --- p.107 / Chapter 4.4 --- Regulation of BRE promoter by culture condition --- p.110 / Chapter 4.4.1 --- Cell density --- p.110 / Chapter 4.4.2 --- Serum deprivation --- p.114 / Chapter 4.5 --- Regulation of BRE promoter by kinase inhibitors --- p.120 / Chapter Chapter Five: --- BRE and cell cycle analysis --- p.127 / Chapter 5.1 --- Cell synchronization in G1 phase by aphidicolin (APC) --- p.127 / Chapter 5.1.1 --- Flow analysis --- p.128 / Chapter 5.1.2 --- Luciferase reporter assay --- p.128 / Chapter 5.1.3 --- Western blot analysis --- p.129 / Chapter 5.2 --- Cell synchronization in G2/M phase by colchicine (COL) --- p.137 / Chapter 5.2.1 --- Flow analysis --- p.137 / Chapter 5.2.2 --- Luciferase reporter assay --- p.137 / Chapter 5.2.3 --- Western blot analysis --- p.138 / Chapter 5.3 --- Cell cycle analysis of the treatments investigated by luciferase assays --- p.144 / Chapter Chapter Six: --- Discussion --- p.149 / Chapter 6.1 --- Study of BRE expression --- p.149 / Chapter 6.2 --- Study of BRE regulation --- p.154 / Chapter 6.3 --- Conclusion --- p.163 / Reference --- p.164 / Appendix (Raw data and statistical information of luciferase assays)

Yiu Wai Han. / "June 2003." / Thesis (Ph.D.)--Chinese University of Hong Kong, 2003. / Includes bibliographical references (p. 146-156) / Electronic reproduction. Hong Kong : Chinese University of Hong Kong, [2012] System requirements: Adobe Acrobat Reader. Available via World Wide Web. / Mode of access: World Wide Web. / Abstracts in English and Chinese.

Thesis (Ph. D.)--University of Washington, 2001. / Vita. Includes bibliographical references (leaves 105-135).

Diss. (sammanfattning) Stockholm : Karolinska institutet, 2009.

Diss. (sammanfattning) Umeå : Umeå universitet, 2010. / Härtill 2 uppsatser.

Thesis (Ph.D.)--University of Alabama at Birmingham, 2007. / Title from PDF title page (viewed on Feb. 19, 2010). Includes bibliographical references.

Dissertation (Ph.D.)--University of South Florida, 2008. / Includes vita. Includes bibliographical references.

Diss. (sammanfattning) Stockholm : Karolinska institutet, 2009. / Härtill 4 uppsatser.

Dissertation (Ph.D.)--University of South Florida, 2008. / Includes vita. Includes bibliographical references. Also available online.

The Cbl family of E3 ubiquitin ligases are important negative regulators of multiple receptor and cytoplasmic tyrosine kinases, and participate in a wide variety of cellular processes. Uncoupling of Cbl-mediated negative regulation allows activated receptor tyrosine kinases such as the Met receptor to escape degradation, enhancing their oncogenic potential in vitro and in vivo. Despite the consequences of loss of Cbl-mediated negative regulation for human disease, little is known about the mechanisms regulating Cbl protein levels themselves. / In this thesis work, I demonstrate a differential regulation of c-Cbl and Cbl-b downstream of the Met receptor tyrosine kinase. Cbl-b protein levels decrease in response to Met kinase activity, whereas c-Cbl levels remain stable. Cbl-b is partially degraded in a proteasome-dependant manner. This requires Cbl-b ubiquitin ligase activity and a carboxy terminal domain region located between the RING and UBA domains. I conclude that the regulation of c-Cbl and Cbl-b differs downstream of Met, and propose that negative regulation of Cbl-b by a dysregulated Met receptor may contribute to tumourigenesis.