Induction of apoptosis by a secreted lipocalin that is transcriptionally regulated by IL-3 deprivation
Howard Hughes Medical Institute, Program in Molecular Medicine; Program in Gene Function and Expression
Acute-Phase Proteins; Animals; *Apoptosis; Autocrine Communication; Carrier Proteins; Cell Line; Cells, Cultured; Culture Media, Conditioned; Dexamethasone; *Gene Expression Regulation; Humans; Insulin-Like Growth Factor I; Interleukin-3; Interleukins; Leukocytes; Lipocalins; Mice; Oligonucleotide Array Sequence Analysis; Oncogene Proteins; Phosphorylation; Proto-Oncogene Proteins; Proto-Oncogene Proteins c-bcl-2; Receptors, Cell Surface; Recombinant Fusion Proteins; Transcription, Genetic; Tumor Cells, Cultured; bcl-Associated Death Protein; bcl-X Protein
Life Sciences | Medicine and Health Sciences
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.
DOI of Published Version
Science. 2001 Aug 3;293(5531):829-34. Link to article on publisher's site
Science (New York, N.Y.)
Devireddy, Laxminarayana R.; Teodoro, Jose G.; Richard, Fabien A.; and Green, Michael R., "Induction of apoptosis by a secreted lipocalin that is transcriptionally regulated by IL-3 deprivation" (2001). Open Access Articles. 1636.