? ? The regulation of programmed cell death, or apoptosis, plays a critical role in both normal development and in the maintenance of adult tissues. Survival factors that prevent apoptosis act in the normal course of development, or, when inappropriately applied, contribute to pathologies such as cancer or neurodegeneration. Many extracellular survival signals, such as growth factors, stimulate receptor tyrosine kinases at the cell surface. These signals then propagate to intracellular second messenger targets. The PI 3-kinase pathway regulates a variety of transcription factors via the phosphorylation of its downstream effectors Akt and GSK-3B. Akt and GSK-313 may contribute to the control of programmed cell death by regulating gene expression at the transcriptional level. These transcription factors can initiate programs that are either pro- or anti-apoptotic. Studies have begun to elucidate the genes affected by these pathways, however the gene targets of PI 3-kinase/Akt/GSK-36 signaling remain undefined. DNA microarrays will be employed to profile the transcriptional effects of this pathway in growth factor stimulated cells. Inhibitors of PI 3-kinase/Akt and GSK-36 will identify those genes specific to each pathway. Genes identified as targets of PI 3-kinase/Akt and MEK will be assessed for common cis-elements using computational tools. Predicted cis-elements will then be tested by chromatin immunoprecipitation. ? ? ?

Agency
National Institute of Health (NIH)
Institute
National Institute of General Medical Sciences (NIGMS)
Type
Postdoctoral Individual National Research Service Award (F32)
Project #
1F32GM067392-01A1
Application #
6693182
Study Section
Special Emphasis Panel (ZRG1-F05 (20))
Program Officer
Wolfe, Paul B
Project Start
2003-09-01
Project End
2005-08-31
Budget Start
2003-09-01
Budget End
2004-08-31
Support Year
1
Fiscal Year
2003
Total Cost
$46,420
Indirect Cost
Name
Boston University
Department
Biology
Type
Schools of Arts and Sciences
DUNS #
049435266
City
Boston
State
MA
Country
United States
Zip Code
02215