Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
19
pubmed:dateCreated
2000-6-7
pubmed:abstractText
BCL-2 family proteins play a central role in apoptosis regulation in mammals and in C. elegans. Mammalian cellular and viral anti-apoptosis proteins such as BCL-2 and E1B-19K interact with several cellular proteins. Some of these interacting proteins promote apoptosis and belong to the BCL-2 family. Certain BCL-2 family proapoptotic proteins such as BAX and BAK share extensive sequence homology with BCL-2. In contrast, certain pro-apoptotic proteins such as BIK and BID share a single death effector domain, BH3, with other BCL-2 family proteins. By mutational analysis, we show that one of the cellular proteins, BNIP1 (previously Nip-1), that interacts with BCL-2 family anti-apoptosis proteins is a 'BH3 alone' pro-apoptotic protein. Transient transfection of BNIP1 induces a moderate level of apoptosis. Deletions of the N-terminal 32 amino acid region and the C-terminal trans-membrane domain did not significantly affect pro-apoptotic activity. In contrast, deletions encompassing a region containing a motif similar to the BH3-domain abrogated the apoptotic activity. Substitution of BNIP1 BH3 domain for the corresponding sequence in BAX efficiently restored the apoptotic activity of BAX, establishing the functional identity of the BH3 domain of BNIP1. The N-terminal deletions of BNIP1 (that retain the BH3 domain) enhanced the level of interaction with BCL-XL. Mutants containing the BH3 deletions were still able to heterodimerize with BCL-XL while mutants lacking both the N-terminal region and the BH3 domain were unable to heterodimerize, suggesting that BNIP1 may bind to BCL-XL via two different binding motifs.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
http://linkedlifedata.com/resource/pubmed/chemical/Apoptosis Regulatory Proteins, http://linkedlifedata.com/resource/pubmed/chemical/BAX protein, human, http://linkedlifedata.com/resource/pubmed/chemical/BCL2L1 protein, human, http://linkedlifedata.com/resource/pubmed/chemical/BIK protein, human, http://linkedlifedata.com/resource/pubmed/chemical/BNIP1 protein, human, http://linkedlifedata.com/resource/pubmed/chemical/Membrane Proteins, http://linkedlifedata.com/resource/pubmed/chemical/Proteins, 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-Associated X Protein, http://linkedlifedata.com/resource/pubmed/chemical/bcl-X Protein
pubmed:status
MEDLINE
pubmed:month
May
pubmed:issn
0950-9232
pubmed:author
pubmed:issnType
Print
pubmed:day
4
pubmed:volume
19
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
2363-7
pubmed:dateRevised
2007-11-14
pubmed:meshHeading
pubmed:year
2000
pubmed:articleTitle
Functional identification of the apoptosis effector BH3 domain in cellular protein BNIP1.
pubmed:affiliation
Institute for Molecular Virology, St Louis University Medical Center, MO 63110, USA.
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, P.H.S., Research Support, Non-U.S. Gov't