Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
26
pubmed:dateCreated
2004-6-21
pubmed:abstractText
Human neutrophils normally have a very short half-life and die by apoptosis. Cytokines such as granulocyte-macrophage colony-stimulating factor (GM-CSF) can delay this apoptosis via increases in the cellular levels of Mcl-1, an anti-apoptotic protein of the Bcl-2 family with a rapid turnover rate. Here we have shown that inhibition of the proteasome (a) decreases the rate of Mcl-1 turnover within neutrophils and (b) significantly delays apoptosis. This led us to determine whether GM-CSF could enhance neutrophil survival by altering the rate of Mcl-1 turnover. Addition of GM-CSF to neutrophils enhanced Mcl-1 stability and delayed apoptosis by signaling pathways requiring PI3K/Akt and p44/42 Erk/Mek, because inhibitors of these pathways completely abrogated the GM-CSF-mediated effect on both Mcl-1 stability and apoptosis delay. Conversely, induction of Mcl-1 hyperphosphorylation by the phosphatase inhibitor, okadaic acid, significantly accelerated both Mcl-1 turnover and apoptosis. Neither the calpain inhibitor, carbobenzoxy-valinyl-phenylalaninal, nor the pan caspase inhibitor, benzyloxycarbonyl-VAD-fluoromethylketone, had any effect on Mcl-1 stability under these conditions. These observations indicate that profound changes in the rate of neutrophil apoptosis following cytokine signaling occur via dynamic changes in the rate of Mcl-1 turnover via the proteasome.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
http://linkedlifedata.com/resource/pubmed/chemical/AKT1 protein, human, http://linkedlifedata.com/resource/pubmed/chemical/Calpain, http://linkedlifedata.com/resource/pubmed/chemical/Caspases, http://linkedlifedata.com/resource/pubmed/chemical/Cycloheximide, http://linkedlifedata.com/resource/pubmed/chemical/Cysteine Endopeptidases, http://linkedlifedata.com/resource/pubmed/chemical/Cysteine Proteinase Inhibitors, http://linkedlifedata.com/resource/pubmed/chemical/Enzyme Inhibitors, http://linkedlifedata.com/resource/pubmed/chemical/Granulocyte-Macrophage..., http://linkedlifedata.com/resource/pubmed/chemical/Leupeptins, http://linkedlifedata.com/resource/pubmed/chemical/Mitogen-Activated Protein Kinases, http://linkedlifedata.com/resource/pubmed/chemical/Multienzyme Complexes, http://linkedlifedata.com/resource/pubmed/chemical/Neoplasm Proteins, http://linkedlifedata.com/resource/pubmed/chemical/Phosphatidylinositol 3-Kinases, http://linkedlifedata.com/resource/pubmed/chemical/Phosphoric Monoester Hydrolases, http://linkedlifedata.com/resource/pubmed/chemical/Proteasome Endopeptidase Complex, http://linkedlifedata.com/resource/pubmed/chemical/Protein Synthesis Inhibitors, http://linkedlifedata.com/resource/pubmed/chemical/Protein-Serine-Threonine Kinases, http://linkedlifedata.com/resource/pubmed/chemical/Proto-Oncogene Proteins, http://linkedlifedata.com/resource/pubmed/chemical/Proto-Oncogene Proteins c-akt, http://linkedlifedata.com/resource/pubmed/chemical/Proto-Oncogene Proteins c-bcl-2, http://linkedlifedata.com/resource/pubmed/chemical/benzyloxycarbonylleucyl-leucyl-leuci..., http://linkedlifedata.com/resource/pubmed/chemical/myeloid cell leukemia sequence 1...
pubmed:status
MEDLINE
pubmed:month
Jun
pubmed:issn
0021-9258
pubmed:author
pubmed:issnType
Print
pubmed:day
25
pubmed:volume
279
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
26915-21
pubmed:dateRevised
2010-11-18
pubmed:meshHeading
pubmed-meshheading:15078892-Apoptosis, pubmed-meshheading:15078892-Calpain, pubmed-meshheading:15078892-Caspases, pubmed-meshheading:15078892-Cycloheximide, pubmed-meshheading:15078892-Cysteine Endopeptidases, pubmed-meshheading:15078892-Cysteine Proteinase Inhibitors, pubmed-meshheading:15078892-Enzyme Activation, pubmed-meshheading:15078892-Enzyme Inhibitors, pubmed-meshheading:15078892-Granulocyte-Macrophage Colony-Stimulating Factor, pubmed-meshheading:15078892-Humans, pubmed-meshheading:15078892-Leupeptins, pubmed-meshheading:15078892-Mitogen-Activated Protein Kinases, pubmed-meshheading:15078892-Multienzyme Complexes, pubmed-meshheading:15078892-Neoplasm Proteins, pubmed-meshheading:15078892-Neutrophils, pubmed-meshheading:15078892-Phosphatidylinositol 3-Kinases, pubmed-meshheading:15078892-Phosphoric Monoester Hydrolases, pubmed-meshheading:15078892-Proteasome Endopeptidase Complex, pubmed-meshheading:15078892-Protein Synthesis Inhibitors, pubmed-meshheading:15078892-Protein-Serine-Threonine Kinases, pubmed-meshheading:15078892-Proto-Oncogene Proteins, pubmed-meshheading:15078892-Proto-Oncogene Proteins c-akt, pubmed-meshheading:15078892-Proto-Oncogene Proteins c-bcl-2, pubmed-meshheading:15078892-Signal Transduction
pubmed:year
2004
pubmed:articleTitle
Granulocyte macrophage colony-stimulating factor signaling and proteasome inhibition delay neutrophil apoptosis by increasing the stability of Mcl-1.
pubmed:affiliation
School of Biological Sciences, Biosciences Building and Department of Medicine, University of Liverpool, Liverpool L69 7ZB, United Kingdom.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't