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T-Space at The University of Toronto Libraries >
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Please use this identifier to cite or link to this item: http://hdl.handle.net/1807/18227

Title: A Novel Role for Tid1 in HIF2α Regulation
Authors: Burnett, David
Advisor: Rozakis-Adcock, Maria
Department: Laboratory Medicine and Pathobiology
Keywords: Tid1
HIF
renal cell carcinoma
hypoxia inducible factor
VHL
von Hippel Lindau
Issue Date: 11-Jan-2010
Abstract: 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.
URI: http://hdl.handle.net/1807/18227
Appears in Collections:Master
Department of Laboratory Medicine and Pathobiology - Master theses

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