PUMA cooperates with direct activator proteins to promote mitochondrial outer membrane permeabilization and apoptosis.
The BCL-2 family of proteins regulates apoptosis by controlling mitochondrial outer membrane permeabilization (MOMP). Within the family there are numerous protein-protein interactions that influence MOMP; however, defining the ultimate signal that commits a cell to apoptosis remains controversial. We chose to examine the function of the BH3-only protein, p53 upregulated modulator of apoptosis (PUMA), to define its contribution to MOMP and cooperation with the direct activator proteins. PUMA is a potent regulator of MOMP and our data suggest that this function is attributed to two distinct mechanisms which both rely on PUMA binding to the anti-apoptotic BCL-2 proteins: de-repression and sensitization. Here we will define these interactions and discuss our experiments that suggest PUMA cooperates with direct activator proteins to efficiently induce MOMP and apoptosis.
Chipuk
Jerry E
JE
Department of Immunology, St. Jude Children's Research Hospital, Memphis, TN 38105, USA.
Green
Douglas R
DR
D017209:Apoptosis; D051017:Apoptosis Regulatory Proteins / Q000378:metabolism*; D006801:Humans; D051336:Mitochondrial Membranes / Q000378:metabolism*; D010539:Permeability; D011485:Protein Binding; D017434:Protein Structure, Tertiary; D011518:Proto-Oncogene Proteins / Q000378:metabolism*; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism
D051017:Apoptosis Regulatory Proteins; C438378:BBC3 protein, human; D011518:Proto-Oncogene Proteins; D019253:Proto-Oncogene Proteins c-bcl-2; D016159:Tumor Suppressor Protein p53