Editors' ChoiceApoptosis

Death by Deprivation

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Science's STKE  07 Aug 2001:
Vol. 2001, Issue 94, pp. tw13
DOI: 10.1126/stke.2001.94.tw13

Many hematopoietic cells die by apoptosis when deprived of specific cytokines, and this process requires active transcription. Using DNA microarrays to identify specific genes that are transcriptionally activated after cytokine withdrawal, Devireddy et al. discovered an important new player in this cell death pathway. In a study of interleukin-3 (IL-3)-dependent murine FL5.12 pro-B cells, they find that the gene showing maximal transcriptional activation upon IL-3 withdrawal is 24p3. The 24p3 gene encodes a small secreted protein with sequence motifs characteristic of lipocalins, a large family of proteins previously linked to diverse functions ranging from retinol transport to prostaglandin synthesis to modulation of the immune response. Addition of 24p3 to the culture medium induced apoptosis of a wide variety of leukocytes, and apoptotic sensitivity appeared to be determined by the presence or absence of a cell surface receptor for 24p3.

L. R. Devireddy, J. G. Teodoro, F. A. Richard, M. R. Green, Induction of apoptosis by a secreted lipocalin that is transcriptionally regulated by IL-3 deprivation. Science 293, 829-834 (2001). [Abstract] [Full Text]

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