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http://purl.uniprot.org/citations/16443602http://www.w3.org/1999/02/22-rdf-syntax-ns#typehttp://purl.uniprot.org/core/Journal_Citation
http://purl.uniprot.org/citations/16443602http://www.w3.org/2000/01/rdf-schema#comment"The induction of apoptosis by p53 in response to cellular stress is its most conserved function and crucial for p53 tumor suppression. We recently reported that p53 directly induces oligomerization of the BH1,2,3 effector protein Bak, leading to outer mitochondrial membrane permeabilization (OMMP) with release of apoptotic activator proteins. One important mechanism by which p53 achieves OMMP is by forming an inhibitory complex with the anti-apoptotic BclXL protein. In contrast, the p53 complex with the Bcl2 homolog has not been interrogated. Here we have undertaken a detailed characterization of the p53-Bcl2 interaction using structural, biophysical, and mutational analyses. We have identified the p53 DNA binding domain as the binding interface for Bcl2 using solution NMR. The affinity of the p53-Bcl2 complex was determined by surface plasmon resonance analysis (BIAcore) to have a dominant component KD 535 +/-24 nm. Moreover, in contrast to wild type p53, endogenous missense mutants of p53 are unable to form complexes with endogenous Bcl2 in human cancer cells. Functionally, these mutants are all completely or strongly compromised in mediating OMMP, as measured by cytochrome c release from isolated mitochondria. These data implicate p53-Bcl2 complexes in contributing to the direct mitochondrial p53 pathway of apoptosis and further support the notion that the DNA binding domain of p53 is a dual function domain, mediating both its transactivation function and its direct mitochondrial apoptotic function."xsd:string
http://purl.uniprot.org/citations/16443602http://purl.org/dc/terms/identifier"doi:10.1074/jbc.m507611200"xsd:string
http://purl.uniprot.org/citations/16443602http://purl.uniprot.org/core/author"Klein C."xsd:string
http://purl.uniprot.org/citations/16443602http://purl.uniprot.org/core/author"Kessler H."xsd:string
http://purl.uniprot.org/citations/16443602http://purl.uniprot.org/core/author"Pan H."xsd:string
http://purl.uniprot.org/citations/16443602http://purl.uniprot.org/core/author"Tomita Y."xsd:string
http://purl.uniprot.org/citations/16443602http://purl.uniprot.org/core/author"Nemajerova A."xsd:string
http://purl.uniprot.org/citations/16443602http://purl.uniprot.org/core/author"Moll U.M."xsd:string
http://purl.uniprot.org/citations/16443602http://purl.uniprot.org/core/author"Erster S."xsd:string
http://purl.uniprot.org/citations/16443602http://purl.uniprot.org/core/author"Marchenko N."xsd:string
http://purl.uniprot.org/citations/16443602http://purl.uniprot.org/core/author"Pancoska P."xsd:string
http://purl.uniprot.org/citations/16443602http://purl.uniprot.org/core/author"Dehner A."xsd:string
http://purl.uniprot.org/citations/16443602http://purl.uniprot.org/core/date"2006"xsd:gYear
http://purl.uniprot.org/citations/16443602http://purl.uniprot.org/core/name"J Biol Chem"xsd:string
http://purl.uniprot.org/citations/16443602http://purl.uniprot.org/core/pages"8600-8606"xsd:string
http://purl.uniprot.org/citations/16443602http://purl.uniprot.org/core/title"WT p53, but not tumor-derived mutants, bind to Bcl2 via the DNA binding domain and induce mitochondrial permeabilization."xsd:string
http://purl.uniprot.org/citations/16443602http://purl.uniprot.org/core/volume"281"xsd:string
http://purl.uniprot.org/citations/16443602http://www.w3.org/2004/02/skos/core#exactMatchhttp://purl.uniprot.org/pubmed/16443602
http://purl.uniprot.org/citations/16443602http://xmlns.com/foaf/0.1/primaryTopicOfhttps://pubmed.ncbi.nlm.nih.gov/16443602
http://purl.uniprot.org/uniprot/P10415#attribution-35FAC57521C9AAE9EE252BA54633A934http://purl.uniprot.org/core/sourcehttp://purl.uniprot.org/citations/16443602
http://purl.uniprot.org/uniprot/#_A0A087WXZ1-mappedCitation-16443602http://www.w3.org/1999/02/22-rdf-syntax-ns#objecthttp://purl.uniprot.org/citations/16443602
http://purl.uniprot.org/uniprot/#_A0A087X1Q1-mappedCitation-16443602http://www.w3.org/1999/02/22-rdf-syntax-ns#objecthttp://purl.uniprot.org/citations/16443602
http://purl.uniprot.org/uniprot/#_A0A0C4KX50-mappedCitation-16443602http://www.w3.org/1999/02/22-rdf-syntax-ns#objecthttp://purl.uniprot.org/citations/16443602
http://purl.uniprot.org/uniprot/#_A0A1L4AQQ4-mappedCitation-16443602http://www.w3.org/1999/02/22-rdf-syntax-ns#objecthttp://purl.uniprot.org/citations/16443602