Publication Abstract from PubMed
Under conditions of genotoxic stress, human p53 activates the apoptotic effectors BAX or BAK to result in mitochondrial outer-membrane permeabilization and apoptosis. Antiapoptotic BCL-2 family member BCL-xL opposes this activity by sequestering cytosolic p53 via association with its DNA-binding domain, an interaction enhanced by p53 tetramerization. Here we characterized the BCL-xL-p53 complex by NMR spectroscopy and modulated it through mutagenesis to determine the relative contributions of BCL-xL's interactions with p53 or other BCL-2 family proteins to the BCL-xL-dependent inhibition of UV irradiation-induced apoptosis. Under our experimental conditions, one-third of the antiapoptotic activity of BCL-xL was mediated by p53 sequestration and the remaining two-thirds through sequestration of proapoptotic BCL-2 family members. Our studies define the contributions of cytosolic p53 to UV irradiation-induced apoptosis and provide opportunities to explore its contributions to other p53-dependent apoptotic signaling pathways.
The DNA-binding domain mediates both nuclear and cytosolic functions of p53.,Follis AV, Llambi F, Ou L, Baran K, Green DR, Kriwacki RW Nat Struct Mol Biol. 2014 Jun;21(6):535-43. doi: 10.1038/nsmb.2829. Epub 2014 May, 11. PMID:24814347[1]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
