TITLE

p53-MEDIATEDCELL CYCLE ARREST AND APOPTOSIS

AUTHOR(S)
Yunping LIN; BENCHIMOL, Sam
PUB. DATE
April 1997
SOURCE
Leukemia (08876924);Apr97 Supplement 3, Vol. 11, p324
SOURCE TYPE
Academic Journal
DOC. TYPE
Conference Paper
ABSTRACT
We have generated a series of routine erythroleukemia clones that ectopically express a temperature sensitive mutant p53 allele. In many clones, activation of p53 at low temperature resulted in the accumulation of cells in GI and in apoptosis. Several cytokines including erythropoietin, IL-3 and the ligand for the Kit receptor blocked p53-dependent apoptosis in p53ts-expressing cells at 32°C. Cytokine-treated cells were reversibly arrested in G1 and resumed growth upon return to 37°C. Certain clones exhibited only a GI arrest in response to p53 activation at 32°C. One of these clones secreted erythropoietin and another secreted IL-3. We tested the possibility that autocrine secretion of IL-3 played a role in preventing apoptosis and showed that disruption of the autocrine loop by cell dilution or with neutralizing antibodies to IL-3 restored p53-dependent apoptosis at 32°C. Thus, two properties of p53 protein, namely, its ability to arrest cells in G1 and its ability to promote apoptosis could be uncoupled by cytokines acting as survival factors.
ACCESSION #
34696178

 

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