| Project
Description: |
The theme of this Program
Project application is to understand the signal transduction
pathways mediating ischemic injury and cardioprotection using a
multidisciplinary approach combining biophysics, physiology,
proteomics and genetics. While Projects 1-3 are focused on two
signaling pathways previously known to modulate ischemic injury and
protection (i.e., PKCe and p38 MAPK), Project 4 focuses on a pathway
with recently recognized importance in the field of myocardial
ischemia-cell cycle regulatory proteins. It will focus on three
molecules in particular whose functions are interrelated: cyclin-dependent
kinase-2 (Cdk2), the retinoblastoma gene product (Rb), and E2Fs
transcription factors that regulate genes responsible for cell cycle
entry including Cyclin A and E, the catalytic partners of Cdk2. The
proposed investigations will make key contributions to understanding
the molecular basis for Rb's cardioprotective effect in the setting
of ischemia/reperfusion injury and the mechanism(s) underlying
Cdk2's ability to regulate ischemic damage and apoptotic cell death. |
