Global ETD Search

1	Differential regulation of c-Cbl and Cbl-b ubiquitin ligases downstream of the Met receptor tyrosine kinase Durrant, Michael, 1982- January 2007 (has links) 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. Gene Expression Regulation, Neoplastic. Ubiquitin-Protein Ligases -- metabolism.
2	Differential regulation of c-Cbl and Cbl-b ubiquitin ligases downstream of the Met receptor tyrosine kinase Durrant, Michael, 1982- January 2007 (has links) No description available. Ubiquitin-Protein Ligases -- metabolism. Gene Expression Regulation, Neoplastic.
3	Cbx4 regulates the proliferation of thymic epithelial cells and thymus function Liu, B., Liu, Y. F., Du, Y. R., Mardaryev, A. N., Yang, W., Chen, H., Xu, Z. M., Xu, C. Q., Zhang, X. R., Botchkarev, V. A., Zhang, Y., Xu, G. L. January 2013 (has links) Thymic epithelial cells (TECs) are the main component of the thymic stroma, which supports T-cell proliferation and repertoire selection. Here, we demonstrate that Cbx4, a Polycomb protein that is highly expressed in the thymic epithelium, has an essential and non-redundant role in thymic organogenesis. Targeted disruption of Cbx4 causes severe hypoplasia of the fetal thymus as a result of reduced thymocyte proliferation. Cell-specific deletion of Cbx4 shows that the compromised thymopoiesis is rooted in a defective epithelial compartment. Cbx4-deficient TECs exhibit impaired proliferative capacity, and the limited thymic epithelial architecture quickly deteriorates in postnatal mutant mice, leading to an almost complete blockade of T-cell development shortly after birth and markedly reduced peripheral T-cell populations in adult mice. Furthermore, we show that Cbx4 physically interacts and functionally correlates with p63, which is a transcriptional regulator that is proposed to be important for the maintenance of the stemness of epithelial progenitors. Together, these data establish Cbx4 as a crucial regulator for the generation and maintenance of the thymic epithelium and, hence, for thymocyte development. Animals Bromodeoxyuridine Cell Proliferation Epithelial Cells/metabolism/physiology Flow Cytometry Gene Targeting Histological Techniques Immunoprecipitation Mice Microscopy, Fluorescence Organogenesis/physiology Phosphoproteins/metabolism Real-Time Polymerase Chain Reaction T-Lymphocytes/cytology Thymus Gland/cytology/embryology Trans-Activators/metabolism Ubiquitin-Protein Ligases/*metabolism REF 2014

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