This research proposal addresses the mechanism/s leading to cell death upon inactivation of CTP: phosphocholine cytidylyltranferase (CCT) the main regulatory enzyme of the phosphatidylcholine synthesizing pathway. Our own previous results show a close correlation between the inhibitory potency towards CCt activity of various synthetic ceramides abd antitumor alkyl-lysophospholids and their cytotoxicity, making this enzyme a very promising pharmacological target for the development of new antitumor molecules. As these drugs are known to affect signalling cascades related to cell survival- MEK-ERK, Akt, etc..) either because of direct inhibition or secondarily to their primary action on CCt, wepropose a detailed characterization of molecular events during cell death taking place at a restrictive temperature in the CHO MT-58 cell line. Which expresses a termolabile CCt. This will enable us to separate antitumo effects acting on pharmacological targets other thatn CCt from effects secondary to CCt inhibition. Based on this rationale, we propose the following specific aims
|Effective start/end date||13/12/04 → 13/12/07|
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