Induction of apoptosis by a secreted lipocalin that is transcriptionally regulated by IL-3 deprivation.
Many hematopoietic cells undergo apoptosis when deprived of specific cytokines, and this process requires de novo RNA/protein synthesis. Using DNA microarrays to analyze interleukin-3 (IL-3)-dependent murine FL5.12 pro-B cells, we found that the gene undergoing maximal transcriptional induction after cytokine withdrawal is 24p3, which encodes a secreted lipocalin. Conditioned medium from IL-3-deprived FL5.12 cells contained 24p3 and induced apoptosis in naive FL5.12 cells even when IL-3 was present. 24p3 also induced apoptosis in a wide variety of leukocytes but not other cell types. Apoptotic sensitivity correlated with the presence of a putative 24p3 cell surface receptor. We conclude that IL-3 deprivation activates 24p3 transcription, leading to synthesis and secretion of 24p3, which induces apoptosis through an autocrine pathway.
Devireddy
L R
LR
Howard Hughes Medical Institute, Program in Gene Function and Expression and Program in Molecular Medicine, University of Massachusetts Medical School, 373 Plantation Street, Worcester, MA 01605, USA.
Teodoro
J G
JG
Richard
F A
FA
Green
M R
MR
D000209:Acute-Phase Proteins / Q000235:genetics* / Q000378:metabolism*; D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D019898:Autocrine Communication; D002352:Carrier Proteins / Q000378:metabolism; D002460:Cell Line; D002478:Cells, Cultured; D017077:Culture Media, Conditioned; D003907:Dexamethasone / Q000494:pharmacology; D005786:Gene Expression Regulation; D006801:Humans; D007334:Insulin-Like Growth Factor I / Q000494:pharmacology; D007377:Interleukin-3 / Q000378:metabolism*; D007378:Interleukins / Q000378:metabolism; D007962:Leukocytes / Q000166:cytology / Q000502:physiology*; D000071068:Lipocalin-2; D054834:Lipocalins; D051379:Mice; D020411:Oligonucleotide Array Sequence Analysis; D015513:Oncogene Proteins / Q000235:genetics* / Q000378:metabolism*; D010766:Phosphorylation; D011518:Proto-Oncogene Proteins; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism; D011956:Receptors, Cell Surface / Q000378:metabolism; D011993:Recombinant Fusion Proteins / Q000378:metabolism; D014158:Transcription, Genetic; D014407:Tumor Cells, Cultured; D051025:bcl-Associated Death Protein; D051020:bcl-X Protein
D000209:Acute-Phase Proteins; C494819:BAD protein, human; C494811:BCL2L1 protein, human; C494820:Bad protein, mouse; C494812:Bcl2l1 protein, mouse; D002352:Carrier Proteins; D017077:Culture Media, Conditioned; D007377:Interleukin-3; D007378:Interleukins; C489506:LCN2 protein, human; D000071068:Lipocalin-2; D054834:Lipocalins; D015513:Oncogene Proteins; D011518:Proto-Oncogene Proteins; D019253:Proto-Oncogene Proteins c-bcl-2; D011956:Receptors, Cell Surface; D011993:Recombinant Fusion Proteins; D051025:bcl-Associated Death Protein; D051020:bcl-X Protein; C071332:Lcn2 protein, mouse; D007334:Insulin-Like Growth Factor I; D003907:Dexamethasone