Research Article

Induction of Apoptosis by a Secreted Lipocalin That is Transcriptionally Regulated by IL-3 Deprivation

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Science  03 Aug 2001:
Vol. 293, Issue 5531, pp. 829-834
DOI: 10.1126/science.1061075

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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 naı̈ve 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 24p3transcription, leading to synthesis and secretion of 24p3, which induces apoptosis through an autocrine pathway.

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