A Novel Apoptotic Molecule Bok for the Treatment of Breast Cancer
Abstract
Central to apoptosis is the activation of caspases. One apoptotic pathway that activates caspases is the intrinsic apoptotic pathway, which induces changes in mitochondrial membrane permeability and the release of mitochondrial proteins such as cytochrome C, which binds to the adaptor protein Apaf-1 and in the presence of dATP activates pro-caspase 9. Activated caspase 9 activates caspase 3, leading to apoptosis. The Bcl-2 family of proteins are key regulators of the intrinsic apoptotic pathway. Members of the Bcl-2 family play a pivotal role in regulating apoptosis by controlling the mitochondrial changes associated with the release of cytochrome C. Bcl-2, Bcl-x(sub L), Bcl-w, and Mcl-1 promote cell survival by inhibiting the release of cytochrome C while Bax, Bak THE Bcl-2 Homology BH domains 1-3 group or Bad, Bid, Bik, Bim, Puma, Noxa, and others THE BH3 domain-only group induce cell death by promoting the release of cytochrome C. The BH3 domain-only group serves as sensors of apoptotic signals. Predominantly cytosolic in healthy cells, Bax translocates to the mitochondria in response to an apoptotic stimulus, where it promotes cell death by altering the permeability of the mitochondrial membrane. Bax and Bak demonstrate functional redundancy at the mitochondria in that one (but not both) must be functional for apoptosis-related mitochondrial changes to occur. Recently, associations were noted between the apoptotic functions of Bax and Bak and the release of calcium from the endoplasmic reticulum. Although Bcl-2 and Bcl-x(sub L) have been detected in the membranes of the endoplasmic reticulum, mitochondria, and nucleus, their major function is at the mitochondrial membrane, where they oppose the mitochondrial changes initiated by Bax or Bak. There is at present no evidence linking nuclear localization of any member of the Bcl-2 family with their anti or pro-apoptotic function.
Document Details
- Document Type
- Technical Report
- Publication Date
- Mar 01, 2005
- Accession Number
- ADA437670
Entities
People
- Geoffrey A. Bartholomeusz
Organizations
- The University of Texas MD Anderson Cancer Center