|
rdf:type |
|
|
lifeskim:mentions |
|
|
pubmed:issue |
4
|
|
pubmed:dateCreated |
2004-2-24
|
|
pubmed:abstractText |
The Bcl-2 family proteins are key regulators of apoptosis in human diseases and cancers. Though known to block apoptosis, Bcl-2 promotes cell death through an undefined mechanism. Here, we show that Bcl-2 interacts with orphan nuclear receptor Nur77 (also known as TR3), which is required for cancer cell apoptosis induced by many antineoplastic agents. The interaction is mediated by the N-terminal loop region of Bcl-2 and is required for Nur77 mitochondrial localization and apoptosis. Nur77 binding induces a Bcl-2 conformational change that exposes its BH3 domain, resulting in conversion of Bcl-2 from a protector to a killer. These findings establish the coupling of Nur77 nuclear receptor with the Bcl-2 apoptotic machinery and demonstrate that Bcl-2 can manifest opposing phenotypes, induced by interactions with proteins such as Nur77, suggesting novel strategies for regulating apoptosis in cancer and other diseases.
|
|
pubmed:grant |
|
|
pubmed:language |
eng
|
|
pubmed:journal |
|
|
pubmed:citationSubset |
IM
|
|
pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/Cytochromes c,
http://linkedlifedata.com/resource/pubmed/chemical/DNA-Binding Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Glutathione Transferase,
http://linkedlifedata.com/resource/pubmed/chemical/Green Fluorescent Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Ligands,
http://linkedlifedata.com/resource/pubmed/chemical/Luminescent Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/NR4A1 protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/Nuclear Receptor Subfamily 4...,
http://linkedlifedata.com/resource/pubmed/chemical/Oligonucleotides, Antisense,
http://linkedlifedata.com/resource/pubmed/chemical/Proto-Oncogene Proteins c-bcl-2,
http://linkedlifedata.com/resource/pubmed/chemical/RNA, Small Interfering,
http://linkedlifedata.com/resource/pubmed/chemical/Receptors, Cytoplasmic and Nuclear,
http://linkedlifedata.com/resource/pubmed/chemical/Receptors, Steroid,
http://linkedlifedata.com/resource/pubmed/chemical/Transcription Factors
|
|
pubmed:status |
MEDLINE
|
|
pubmed:month |
Feb
|
|
pubmed:issn |
0092-8674
|
|
pubmed:author |
|
|
pubmed:issnType |
Print
|
|
pubmed:day |
20
|
|
pubmed:volume |
116
|
|
pubmed:owner |
NLM
|
|
pubmed:authorsComplete |
Y
|
|
pubmed:pagination |
527-40
|
|
pubmed:dateRevised |
2009-11-19
|
|
pubmed:meshHeading |
pubmed-meshheading:14980220-Apoptosis,
pubmed-meshheading:14980220-Cell Death,
pubmed-meshheading:14980220-Cell Line,
pubmed-meshheading:14980220-Cytochromes c,
pubmed-meshheading:14980220-DNA-Binding Proteins,
pubmed-meshheading:14980220-Glutathione Transferase,
pubmed-meshheading:14980220-Green Fluorescent Proteins,
pubmed-meshheading:14980220-Humans,
pubmed-meshheading:14980220-Ligands,
pubmed-meshheading:14980220-Luminescent Proteins,
pubmed-meshheading:14980220-Lymphocytes,
pubmed-meshheading:14980220-Microscopy, Fluorescence,
pubmed-meshheading:14980220-Mitochondria,
pubmed-meshheading:14980220-Mutation,
pubmed-meshheading:14980220-Nuclear Receptor Subfamily 4, Group A, Member 1,
pubmed-meshheading:14980220-Oligonucleotides, Antisense,
pubmed-meshheading:14980220-Phenotype,
pubmed-meshheading:14980220-Protein Binding,
pubmed-meshheading:14980220-Protein Structure, Tertiary,
pubmed-meshheading:14980220-Proto-Oncogene Proteins c-bcl-2,
pubmed-meshheading:14980220-RNA, Small Interfering,
pubmed-meshheading:14980220-Receptors, Cytoplasmic and Nuclear,
pubmed-meshheading:14980220-Receptors, Steroid,
pubmed-meshheading:14980220-Transcription Factors,
pubmed-meshheading:14980220-Transfection,
pubmed-meshheading:14980220-Two-Hybrid System Techniques
|
|
pubmed:year |
2004
|
|
pubmed:articleTitle |
Conversion of Bcl-2 from protector to killer by interaction with nuclear orphan receptor Nur77/TR3.
|
|
pubmed:affiliation |
The Burnham Institute, Cancer Center, 10901 North Torrey Pines Road, La Jolla, CA 92037, USA.
|
|
pubmed:publicationType |
Journal Article,
Research Support, U.S. Gov't, P.H.S.,
Research Support, U.S. Gov't, Non-P.H.S.,
Research Support, Non-U.S. Gov't
|
