Survey
* Your assessment is very important for improving the workof artificial intelligence, which forms the content of this project
* Your assessment is very important for improving the workof artificial intelligence, which forms the content of this project
G protein–coupled receptor wikipedia , lookup
Protein phosphorylation wikipedia , lookup
Protein moonlighting wikipedia , lookup
Protein (nutrient) wikipedia , lookup
Hedgehog signaling pathway wikipedia , lookup
List of types of proteins wikipedia , lookup
Nuclear magnetic resonance spectroscopy of proteins wikipedia , lookup
Research group Tumour Hypoxia In the first line of research in our lab we attempt to understand the molecular pathways that allow tumor cells to survive for long periods of hypoxia. These ?hypoxia-tolerance? mechanisms may become attractive targets for overcoming the problem of hypoxia in cancer. The rate of protein synthesis decreases to ~30% of control levels within 1 hour after the onset of hypoxia. Since protein synthesis is one of the highest energy consuming pathways in hypoxic cells, it is postulated that this decrease serves to conserve energy and thereby promote survival. Furthermore, regulation of protein synthesis affects the expression of certain genes that may also promote hypoxia tolerance. Thus, it is expected that if tumor cells are unable to down-regulate protein synthesis during hypoxia, they should be less tolerant of hypoxia. Our preliminary work has resulted in the identification of two molecular pathways that are important for the regulation of translation during hypoxia, i.e. the unfolded protein response and mTOR. The unfolded protein response consists of 3 parralell signalling pathways, initiated by activation of PERK, ATF6 or IRE-1 respectively. Although the PERK-branch is directly involved in regulation of mRNA synthesis, more evidence is gathered that the other two play important roles in hypoxia-tolerance too. To address this we will interfere on different levels within these cascades. Furthermore, we have shown that a process called autophagy (self-eating) is highly activated during hypoxia. It is unclear whether this mechanism is activated to remove damaged or obsolete organelles, or is involved in energy-production during this period where it lacks oxygen. Cells unable to complete the full autophagic process are very sensitive towards oxygen deprivation and targeting this pathway may therefore be an opportunity to enhance tumor therapy. To further elucidate the role of autophagy during hypoxia and to find the best suitable target, several proteins in the signalling pathway will be investigated