Participation of Eag1 in tumor relevant pathways

Downie, Bryan

dc.contributor.advisor	Heinrich, Ralf Prof. Dr.	de
dc.contributor.author	Downie, Bryan	de
dc.date.accessioned	2013-01-22T15:49:43Z	de
dc.date.available	2013-01-30T23:50:58Z	de
dc.date.issued	2010-01-12	de
dc.identifier.uri	http://hdl.handle.net/11858/00-1735-0000-000D-F175-E	de
dc.identifier.uri	http://dx.doi.org/10.53846/goediss-3483
dc.format.mimetype	application/pdf	de
dc.language.iso	eng	de
dc.rights.uri	http://creativecommons.org/licenses/by-nc-nd/3.0/	de
dc.title	Participation of Eag1 in tumor relevant pathways	de
dc.type	doctoralThesis	de
dc.contributor.referee	Melchior, Frauke Prof. Dr.	de
dc.date.examination	2009-10-31	de
dc.subject.dnb	570 Biowissenschaften, Biologie	de
dc.subject.gok	WA	de
dc.description.abstracteng	Ether--go-go-1 (Eag1) is a CNS-localized voltage-gated potassium channel that is found ectopically expressed in a majority of extra-cranial solid tu- mors. While evidence linking Eag1 to tumor biology has been well estab- lished, the mechanisms by which the channel contributes to tumor progres- sion has until recently remained elusive. In this study, we have used in vivo and in vitro techniques to identify Eag1 interactions with HIF-1 regulatory system as a candidate mechanism. Eag1 functionally and physically interacts with HIF prolyl hydoxylases (PHD) and co-immunoprecipitates with ubiquitin and pVHL. Eag1 ubiquitin co- immunoprecipitation is PHD dependent, and Eag1 undergoes proteasomal degradation. Eag1 expression stabilizes HIF and promotes VEGF secretion and angiogenesis in vivo. Our data suggest that Eag1 interferes with the cellular mechanism for main- taining oxygen homeostasis, increasing HIF-1 activity, and thereby VEGF secretion and tumor vascularization.	de
dc.contributor.coReferee	Stühmer, Walter Prof. Dr.	de
dc.subject.topic	Mathematics and Natural Science	de
dc.subject.eng	cancer	de
dc.subject.eng	ion channel	de
dc.subject.eng	angiogenesis	de
dc.subject.eng	hypoxia	de
dc.subject.bk	42.15	de
dc.identifier.urn	urn:nbn:de:gbv:7-webdoc-2333-4	de
dc.identifier.purl	webdoc-2333	de
dc.identifier.ppn	618841172	de

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GZMB - Göttinger Zentrum für molekulare Biowissenschaften [38]
GCMB - Göttingen Center for Molecular Biosciences

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