PUMA BH3 – Other Categories

Apoptosis can be triggered by permeabilization of the mitochondrial membrane leading to leakage of cytochrome c. Work shows this mitochondrial pathway to apoptosis involves pro-apoptotic proteins of the Bcl-2 family including Bak that directly permeabilise the mitochondrial membrane leading to leakage and catastrophic cell damage. The activities of apoptotic proteins are held in check by antiapoptotic paralogs, including Bcl-2. The interactions between these proteins are modulated by BH3-only proteins. BH3 proteins have 9 -15 amino acid BH3 domain and act as direct activators or sensitizers of pro-apoptotic proteins including Bak. PUMA has been identified as a BH3 protein, but its role is less clear. PUMA BH3 peptide provided here is the full 15 residue domain shown to act as a direct activator of Bak activity leading to caspase activity and apoptosis. A direct interaction with Bak has been demonstrated by surface plasmon resonance analysis. Critical data of PUMA and Bak regulation has not been well established. Further work with this peptide may help to clarify the function and role of the PUMA BH3 domain as a direct Bak activator.