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Paul Schlesinger

Washington University in St. Louis
Cell Biology and Physiology
Cell Death Membrane pores and the BCL-2 Family Proteins
Programmed cell death is critical in growth, differentiation and homeostasis of multicellular organisms . The morphologic expression of programmed cell death, apoptosis, has a genetic basis that is clearly dependent on the BCL-2-family proteins. This family of proteins determines an early common decision point in programmed cell death. These proteins insert into membranes, form ion channels and pores that participate in protein translocation. We study membrane activities of the BCL-2-family members from a biophysical perspective. Our studies focus on a central protein of apoptosis, Bax. The insertion of this protein into a bilayer membrane is the determinative step of the apoptotic pathway. Pore and channel formation by this protein requires an in-membrane dimerization followed by a dimerization of dimers, tetramerization, of Bax. These steps are regulated by interactions with anti-apoptotic and BH3-only proteins of the BCl-2 family.
Related File: file134schles06.pdf
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