Minimal XXXX peptides promote cell death by antagonizing anti-apoptotic proteins.

@entity2428 @entity589 @entity588 @entity1836 @entity5353 @entity1835 @entity2424
The pro-apoptotic " @entity2424 domain-only" proteins of the @entity588 family (e.g. @entity5353 and @entity1835 ) transduce multiple death signals to the mitochondrion. They interact with the anti-apoptotic @entity588 family members and induce apoptosis by a mechanism that requires the presence of at least one of the multidomain pro-apoptotic proteins @entity589 or @entity2428 . Although the @entity2424 domain of @entity5353 can promote the pro-apoptotic assembly and function of @entity589 / @entity2428 by itself, other @entity2424 domains do not function as such. The latter point raises the question of whether, and how, these @entity2424 domains induce apoptosis. We show here that a peptide comprising the minimal @entity2424 domain from @entity589 induces apoptosis but is unable to stimulate the apoptotic activity of microinjected recombinant @entity589 . This relies on the inability of the peptide to directly induce @entity589 translocation to mitochondria or a change in its conformation. This peptide nevertheless interferes with @entity589 / @entity1836 interactions in vitro and stimulates the apoptotic activity of @entity589 when combined with @entity1836 . Similarly, a peptide derived from the @entity2424 domain of @entity1835 stimulates @entity589 activity only in the presence of @entity1836 . Thus, @entity2424 domains do not necessarily activate multidomain pro-apoptotic proteins directly but promote apoptosis by releasing active multidomain pro-apoptotic proteins from their anti-apoptotic counterparts.
