Linked Life Data

15869897

Source:http://linkedlifedata.com/resource/pubmed/id/15869897

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
8
pubmed:dateCreated
2005-5-17
pubmed:abstractText
As a single signal, retinoids induce terminal differentiation. This implies that they activate differentiation and apoptosis in a temporally defined order to allow expression of the differentiated phenotype well before death. We report that two apparently contradictory retinoid-induced programs have the capacity to define cellular life span. Anti-apoptotic factors are activated concomitantly with differentiation, while retinoids induce at the same time also pro-apoptotic signaling. We have assessed the roles of two key factors, Bcl2A1 and TRAIL, in the temporal programming of cell death and differentiation. We demonstrate that PLB985 are type II cells in which TRAIL induces apoptosis through the extrinsic and--via Bid activation--also the intrinsic death pathways. Bcl2A1, ectopically over-expressed, or endogenously induced by retinoic acid receptor agonists, protected cells from apoptosis triggered by TRAIL, whose induction required the activation of both the retinoic acid and retinoid X receptors. Bcl2A1 prevented loss of mitochondrial membrane potential and caspase-9, but not caspase-8, activation. The expression of anti-sense Bcl2A1 sensitized PLB985 cells to TRAIL. Co-culture experiments revealed protection from fraternicide if sister cells were pre-exposed to retinoic acid. Collectively, our data support a model in which retinoids orchestrate a life span-regulatory program comprising Bcl2A1 induction to temporally protect against concomitantly induced TRAIL death signaling. Termination of this life span in presence of Bcl2A1 is most likely a consequence of the Bid-independent TRAIL action. Thus, depending on the retinoic acid and retinoid X receptor activation potential of a ligand and the relative efficacies of the intrinsic and extrinsic death pathways in a given cell, a single retinoid triggers the life span of a differentiated phenotype.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Aug
pubmed:issn
1357-2725
pubmed:author
pubmed:issnType
Print
pubmed:volume
37
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
1696-708
pubmed:dateRevised
2006-11-15
pubmed:meshHeading
pubmed-meshheading:15869897-Apoptosis, pubmed-meshheading:15869897-Apoptosis Regulatory Proteins, pubmed-meshheading:15869897-Base Sequence, pubmed-meshheading:15869897-Blotting, Western, pubmed-meshheading:15869897-Cell Aging, pubmed-meshheading:15869897-Coculture Techniques, pubmed-meshheading:15869897-DNA Primers, pubmed-meshheading:15869897-Flow Cytometry, pubmed-meshheading:15869897-Humans, pubmed-meshheading:15869897-Leukemia, pubmed-meshheading:15869897-Membrane Glycoproteins, pubmed-meshheading:15869897-Proto-Oncogene Proteins c-bcl-2, pubmed-meshheading:15869897-Reverse Transcriptase Polymerase Chain Reaction, pubmed-meshheading:15869897-TNF-Related Apoptosis-Inducing Ligand, pubmed-meshheading:15869897-Tretinoin, pubmed-meshheading:15869897-Tumor Cells, Cultured, pubmed-meshheading:15869897-Tumor Necrosis Factor-alpha
pubmed:year
2005
pubmed:articleTitle
Retinoic acid determines life span of leukemic cells by inducing antagonistic apoptosis-regulatory programs.
pubmed:affiliation
Department of Cell Biology and Signal Transduction, Institut de Génétique et de Biologie Moléculaire et Cellulaire/CNRS/INSERM/ULP, BP 10142, F-67404 Illkirch Cedex, C. U. de Strasbourg, France.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't