The carboxyl-terminal sequence of PUMA binds to both anti-apoptotic proteins and membranes.

ABSTRACT: Anti-apoptotic proteins such as BCL-X_L promote cell survival by sequestering pro-apoptotic BCL-2 family members, an activity that frequently contributes to tumorigenesis. Thus, the development of small-molecule inhibitors for anti-apoptotic proteins, termed BH3-mimetics, is revolutionizing how we treat cancer. BH3 mimetics kill cells by displacing sequestered pro-apoptotic proteins to initiate tumor-cell death. Recent evidence has demonstrated that in live cells the BH3-only proteins PUMA and BIM resist displacement by BH3-mimetics, while others like tBID do not. Analysis of the molecular mechanism by which PUMA resists BH3-mimetic mediated displacement from full-length anti-apoptotic proteins (BCL-X_L, BCL-2, BCL-W, and MCL-1) reveals that both the BH3-motif and a nov

SUBMITTER: Pemberton JM 

PROVIDER: S-EPMC10185343 | biostudies-literature | 2023 Apr

REPOSITORIES: biostudies-literature