PDBsum entry 2me8

Apoptosis

PDB id: 2me8

Contents

Protein chain

212 a.a.

References listed in PDB file

Key reference

• Title: The DNA-Binding domain mediates both nuclear and cytosolic functions of p53.
• Authors: A.V.Follis, F.Llambi, L.Ou, K.Baran, D.R.Green, R.W.Kriwacki.
• Ref.: Nat Struct Biol, 2014, 21, 535-543. [DOI no: 10.1038/nsmb.2829]
• PubMed id: 24814347

Abstract

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.