Interference with gene expression induces rapid apoptosis in p53-null T lymphoma cells
- Details
- Publication Year 1999-12,Volume 6,Issue #12,Page 1216-1221
- Journal Title
- CELL DEATH AND DIFFERENTIATION
- Publication Type
- Journal Article
- Abstract
- Two p53-null T lymphoma cell lines proved to be highly sensitive to inhibition of gene expression, With either actinomycin D or cycloheximide, apoptosis commenced within 2 h, as indicated by loss of membrane integrity, degradation of certain proteins (including the phosphatase calcineurin) and DNA fragmentation, These effects were ablated by co-expression of Bcl-2 or co-incubation with the caspase inhibitor Z-VAD-fmk, These results suggest that the apoptotic machinery is in place in these cells but held in check by an unknown labile protein, which probably acts upstream of Bcl-2, Although cycloheximide can activate the JNK or p38 MAP kinases in some cells, neither was implicated here. However, disruption of phosphoinositide 3-kinase signaling may be involved, because the cells were also sensitive to wortmannin, The high sensitivity of the p53-null lymphoma cells to inhibitors of gene expression suggests that such inhibitors might prove useful in the cytotoxic therapy of certain tumors.
- Publisher
- STOCKTON PRESS
- Keywords
- SIGNAL-TRANSDUCTION; DNA FRAGMENTATION; PROTEIN-SYNTHESIS; DEATH; P53; KINASE; BCL-2; BAD; PHOSPHORYLATION; CALCINEURIN
- Publisher's Version
- https://doi.org/10.1038/sj.cdd.4400612
- Terms of Use/Rights Notice
- Refer to copyright notice on published article.
Creation Date: 1999-12-01 12:00:00