Structural Basis for Bcl-2-Regulated Mitochondrion-Dependent Apoptosis
Abstract
The Bcl-2 family proteins are key regulators of programmed cell death, in health and major human diseases, including cancer. Their pro- or anti-apoptotic functions are regulated by subcellular location, as the proteins cycle between soluble and membrane-bound forms; by dimerization with other Bcl-2 family members; by binding to other non-homologous proteins; and by formation of membrane pores that are believed to regulate apoptosis by perturbing mitochondrial physiology. The solution structures of several Bcl-2 family proteins are very similar despite their antagonistic activities, however, the structures of the membrane-associated proteins are not known and may be key to their opposing functions. The goals of this project are: (1) to determine the structures of the membrane-associated Bcl-2 proteins; and (2) to determine their mechanism of apoptosis regulation. The research strategy combines NMR structure determination in lipid environments with biological assays carried out in parallel with structure determination.
Document Details
- Document Type
- Technical Report
- Publication Date
- Apr 01, 2004
- Accession Number
- ADA429719
Entities
People
- Francesca M. Marassi
Organizations
- Sanford Burnham Prebys Medical Discovery Institute