Activity of the hypoxia inducible HIF-alpha transcription factors drive the hypoxic response, resulting in enhancement of angiogenesis, tumour growth, invasion and metastasis. Seeking to uncover a role for Tid1 in control of HIF2-alpha, we used lentiviral shRNA to knock-down Tid1 in 786-0 RCC cells with and without pVHL. In 786-0 cells stably expressing pVHL30, Tid1 knock-down resulted in a dramatic reduction in HIF2-alpha levels relative to controls. Adenoviral-mediated overexpression of Tid1S rescued this decline in HIF2-alpha levels, while overexpression of Tid1L enhanced this decline. A protective role of Tid1S for HIF2-alpha was reproduced in a HEK293 cell model. Immunoprecipitations in HEK293 cells revealed a lack of direct binding between HIF2-alpha and Tid1 in vivo, while adenoviral-mediated overexpression of Tid1 in this model failed to alter in vitro binding between HIF2-alpha and pVHL30. We present a model in which Tid1 regulates HIF2-alpha stability through regulation of pVHL30 nuclear import.
| Identifer | oai:union.ndltd.org:LACETR/oai:collectionscanada.gc.ca:OTU.1807/18227 |
| Date | 11 January 2010 |
| Creators | Burnett, David |
| Contributors | Rozakis-Adcock, Maria |
| Source Sets | Library and Archives Canada ETDs Repository / Centre d'archives des thèses électroniques de Bibliothèque et Archives Canada |
| Language | en_ca |
| Detected Language | English |
| Type | Thesis |
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