Apoptosis is a program of cellular suicide initiated by a wide range of physiological stimuli. While an array of clearly defined changes in cellular morphology accompany apoptosis, the underlying biochemical events which produce cell death are poorly understood. Dr. Kornbluth proposes to use frog (Xenopus) egg extracts to study the signaling pathways which contribute to the regulation of apoptosis. Xenopus eggs contain a vast storehouse of components sufficient to produce 4000 embryonic cells without any growth or input from gene transcription. Therefore, they are a rich source of material which can be used for in vitro reconstitution of cellular processes in a manner which is difficult or impossible in other systems. Using such an in vitro reconstituted, Dr. Kornbluth previously found that the phosphotyrosine-binding adapter protein, crk, is absolutely required for the induction of apoptosis in vitro. to further investigate the apoptotic process in the egg extract, Dr. Kornbluth proposes two specific aims. These are 1) to evaluate the potential role of known-crk-interacting proteins in apoptotic signaling and 2) to identify novel crk-interacting proteins and determine whether they function in apoptotic pathways.

Agency
National Institute of Health (NIH)
Institute
National Institute of General Medical Sciences (NIGMS)
Type
Research Project (R01)
Project #
5R01GM056518-03
Application #
6019368
Study Section
Human Embryology and Development Subcommittee 1 (HED)
Project Start
1997-08-01
Project End
2002-07-31
Budget Start
1999-08-01
Budget End
2000-07-31
Support Year
3
Fiscal Year
1999
Total Cost
Indirect Cost
Name
Duke University
Department
Biochemistry
Type
Schools of Medicine
DUNS #
071723621
City
Durham
State
NC
Country
United States
Zip Code
27705
Nutt, Leta K; Margolis, Seth S; Jensen, Mette et al. (2005) Metabolic regulation of oocyte cell death through the CaMKII-mediated phosphorylation of caspase-2. Cell 123:89-103
Tashker, Jessica S; Olson, Michael; Kornbluth, Sally (2002) Post-cytochrome C protection from apoptosis conferred by a MAPK pathway in Xenopus egg extracts. Mol Biol Cell 13:393-401
Smith, Jesse J; Richardson, D Ashley; Kopf, Jan et al. (2002) Apoptotic regulation by the Crk adapter protein mediated by interactions with Wee1 and Crm1/exportin. Mol Cell Biol 22:1412-23
Olson, M; Kornbluth, S (2001) Mitochondria in apoptosis and human disease. Curr Mol Med 1:91-122
Thress, K; Song, J; Morimoto, R I et al. (2001) Reversible inhibition of Hsp70 chaperone function by Scythe and Reaper. EMBO J 20:1033-41
Smith, J J; Evans, E K; Murakami, M et al. (2000) Wee1-regulated apoptosis mediated by the crk adaptor protein in Xenopus egg extracts. J Cell Biol 151:1391-400
Kaye, F J; Modi, S; Ivanovska, I et al. (2000) A family of ubiquitin-like proteins binds the ATPase domain of Hsp70-like Stch. FEBS Lett 467:348-55
Thress, K; Evans, E K; Kornbluth, S (1999) Reaper-induced dissociation of a Scythe-sequestered cytochrome c-releasing activity. EMBO J 18:5486-93
Kuwana, T; Smith, J J; Muzio, M et al. (1998) Apoptosis induction by caspase-8 is amplified through the mitochondrial release of cytochrome c. J Biol Chem 273:16589-94
Evans, E K; Kornbluth, S (1998) Regulation of apoptosis in Xenopus egg extracts. Adv Enzyme Regul 38:265-80

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