The differential regulation of the transcription factors HIF1α and HIF2α by posttranslational modifications

Abstract

The hypoxia regulated transcription factors HIF-1α and HIF-2α have different targets and are differentially regulated. Literature describes a number of mechanisms that regulate each of the two paralogues in a different way. The aim of this thesis is to provide an overview of how cells distinguish between HIF-1α and 2α regarding regulation of protein activity by posttranslational modifications and interactions with other proteins. We describe five mechanisms, that may serve as a target for genotype based prognosis and therapy. Glut1 which is a downstream target of HIF-α, is used as a candidate epitope to find variable domains of heavy chainonly lama antibodies (VHH)s that bind specifically to cancer cells. In the context of the practical part of this thesis, Glut1 has been isolated of from purified erythrocyte ghosts.