|
rdf:type |
|
|
lifeskim:mentions |
|
|
pubmed:issue |
1
|
|
pubmed:dateCreated |
2001-7-4
|
|
pubmed:abstractText |
Interactions between proteins of the Bcl-2 family play an important role in the regulation of apoptosis. Anti-apoptotic family members can heterodimerize with pro-apoptotic family members and antagonize their function, thus protecting against death. In cells protected from death by overexpression of Bcl-2 much of the Bax is present in Bax/Bcl-2 hetero-multimers and its death signal is blocked as it cannot homodimerize. This led us to use the Bcl-2/Bax heterodimer as a target for new compounds which may provide a therapy particularly suited to tumour cells for which resistance to conventional therapy is associated with elevated expression of Bcl-2. We assessed whether apoptosis could be induced in prostate tumour cells by blocking this heterodimerization with synthetic peptide sequences derived from the BH3 domain of pro-apoptotic Bcl-2 family members. Prostate cells were found to undergo up to 40% apoptosis 48 h following the introduction of synthetic peptides from the BH3 domains of Bax and Bak. The caspase inhibitor z-VAD.fmk provided protection against apoptosis mediated by these peptides. Immunoprecipitation studies revealed that introduction of peptides derived from the BH3 regions of Bak and Bax into cells blocked Bak/Bcl-2 heterodimerization. These data suggest that by blocking the dimerization through which Bcl-2 would normally inhibit apoptosis the apoptotic pathway driven by Bak was re-opened.
|
|
pubmed:commentsCorrections |
http://linkedlifedata.com/resource/pubmed/commentcorrection/11437412-10400666,
http://linkedlifedata.com/resource/pubmed/commentcorrection/11437412-10837473,
http://linkedlifedata.com/resource/pubmed/commentcorrection/11437412-1458483,
http://linkedlifedata.com/resource/pubmed/commentcorrection/11437412-7688182,
http://linkedlifedata.com/resource/pubmed/commentcorrection/11437412-7743383,
http://linkedlifedata.com/resource/pubmed/commentcorrection/11437412-7834748,
http://linkedlifedata.com/resource/pubmed/commentcorrection/11437412-7850782,
http://linkedlifedata.com/resource/pubmed/commentcorrection/11437412-8183370,
http://linkedlifedata.com/resource/pubmed/commentcorrection/11437412-8358790,
http://linkedlifedata.com/resource/pubmed/commentcorrection/11437412-8521816,
http://linkedlifedata.com/resource/pubmed/commentcorrection/11437412-8600029,
http://linkedlifedata.com/resource/pubmed/commentcorrection/11437412-8623925,
http://linkedlifedata.com/resource/pubmed/commentcorrection/11437412-8631771,
http://linkedlifedata.com/resource/pubmed/commentcorrection/11437412-8640809,
http://linkedlifedata.com/resource/pubmed/commentcorrection/11437412-8695785,
http://linkedlifedata.com/resource/pubmed/commentcorrection/11437412-8861942,
http://linkedlifedata.com/resource/pubmed/commentcorrection/11437412-8910926,
http://linkedlifedata.com/resource/pubmed/commentcorrection/11437412-9082997,
http://linkedlifedata.com/resource/pubmed/commentcorrection/11437412-9111042,
http://linkedlifedata.com/resource/pubmed/commentcorrection/11437412-9135020,
http://linkedlifedata.com/resource/pubmed/commentcorrection/11437412-9176486,
http://linkedlifedata.com/resource/pubmed/commentcorrection/11437412-9288188,
http://linkedlifedata.com/resource/pubmed/commentcorrection/11437412-9488720,
http://linkedlifedata.com/resource/pubmed/commentcorrection/11437412-9497329,
http://linkedlifedata.com/resource/pubmed/commentcorrection/11437412-9560217,
http://linkedlifedata.com/resource/pubmed/commentcorrection/11437412-9645223,
http://linkedlifedata.com/resource/pubmed/commentcorrection/11437412-9735050,
http://linkedlifedata.com/resource/pubmed/commentcorrection/11437412-9836559
|
|
pubmed:language |
eng
|
|
pubmed:journal |
|
|
pubmed:citationSubset |
IM
|
|
pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/Amino Acid Chloromethyl Ketones,
http://linkedlifedata.com/resource/pubmed/chemical/BAK1 protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/BAX protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/Caspases,
http://linkedlifedata.com/resource/pubmed/chemical/Cysteine Proteinase Inhibitors,
http://linkedlifedata.com/resource/pubmed/chemical/Membrane Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Oligopeptides,
http://linkedlifedata.com/resource/pubmed/chemical/Peptide Fragments,
http://linkedlifedata.com/resource/pubmed/chemical/Proto-Oncogene Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Proto-Oncogene Proteins c-bcl-2,
http://linkedlifedata.com/resource/pubmed/chemical/bcl-2 Homologous Antagonist-Killer...,
http://linkedlifedata.com/resource/pubmed/chemical/bcl-2-Associated X Protein,
http://linkedlifedata.com/resource/pubmed/chemical/benzyloxycarbonylvalyl-alanyl-aspart...
|
|
pubmed:status |
MEDLINE
|
|
pubmed:month |
Jul
|
|
pubmed:issn |
0007-0920
|
|
pubmed:author |
|
|
pubmed:copyrightInfo |
Copyright 2001 Cancer Research Campaign.
|
|
pubmed:issnType |
Print
|
|
pubmed:day |
6
|
|
pubmed:volume |
85
|
|
pubmed:owner |
NLM
|
|
pubmed:authorsComplete |
Y
|
|
pubmed:pagination |
115-21
|
|
pubmed:dateRevised |
2009-11-18
|
|
pubmed:meshHeading |
pubmed-meshheading:11437412-Amino Acid Chloromethyl Ketones,
pubmed-meshheading:11437412-Amino Acid Sequence,
pubmed-meshheading:11437412-Apoptosis,
pubmed-meshheading:11437412-Blotting, Western,
pubmed-meshheading:11437412-Caspases,
pubmed-meshheading:11437412-Cysteine Proteinase Inhibitors,
pubmed-meshheading:11437412-Dimerization,
pubmed-meshheading:11437412-Electroporation,
pubmed-meshheading:11437412-Humans,
pubmed-meshheading:11437412-Male,
pubmed-meshheading:11437412-Membrane Proteins,
pubmed-meshheading:11437412-Molecular Sequence Data,
pubmed-meshheading:11437412-Oligopeptides,
pubmed-meshheading:11437412-Peptide Fragments,
pubmed-meshheading:11437412-Precipitin Tests,
pubmed-meshheading:11437412-Prostatic Neoplasms,
pubmed-meshheading:11437412-Protein Structure, Tertiary,
pubmed-meshheading:11437412-Proto-Oncogene Proteins,
pubmed-meshheading:11437412-Proto-Oncogene Proteins c-bcl-2,
pubmed-meshheading:11437412-Tumor Cells, Cultured,
pubmed-meshheading:11437412-bcl-2 Homologous Antagonist-Killer Protein,
pubmed-meshheading:11437412-bcl-2-Associated X Protein
|
|
pubmed:year |
2001
|
|
pubmed:articleTitle |
Induction of apoptosis in prostate carcinoma cells by BH3 peptides which inhibit Bak/Bcl-2 interactions.
|
|
pubmed:affiliation |
Dept of Biochemistry, University College Cork, Lee Maltings, Prospect Row, Cork, Ireland.
|
|
pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't
|
