Promyelocytic leukemia protein 4 induces apoptosis by inhibition of survivin expression Journal Article
| Authors: | Xu, Z. X.; Zhao, R. X.; Ding, T.; Tran, T. T.; Zhang, W.; Pandolfi, P. P.; Chang, K. S. |
| Article Title: | Promyelocytic leukemia protein 4 induces apoptosis by inhibition of survivin expression |
| Abstract: | The promyelocytic leukemia protein (PML) plays an essential role in multiple pathways of apoptosis. Our previous study showed that PML enhances tumor necrosis factor-induced apoptosis by inhibiting the NFκB survival pathway. To continue exploring the mechanism of PML-induced apoptosis, we performed a DNA microarray screening of PML target genes using a PML-inducible stable cell line. We found that Survivin was one of the downstream target genes of PML. Cotransfection experiments demonstrated that PML4 repressed transactivation of the Survivin promoter in an isoform-specific manner. Western blot analysis demonstrated that induced PML expression down-regulated Survivin. Inversely, PML knockdown by siRNA up-regulated Survivin expression. A substantial increase in Survivin expression was found in PML-deficient cells. Re-expression of PML in PML-/- mouse embryo fibroblasts down-regulated the expression of Survivin. Furthermore, cells arrested at the G2/M cell cycle phase expressed a high level of Survivin and a significantly lower level of PML. Overexpression of PML in A549 cells reduced Survivin expression leading to massive apoptotic cell death associated with activation of procaspase 9, caspase 3, and caspase 7. Together, our results demonstrate a novel mechanism of PML-induced apoptosis by down-regulation of Survivin. |
| Keywords: | controlled study; protein expression; unclassified drug; human cell; promoter region; nonhuman; proteins; animal cell; mouse; cell cycle; gene overexpression; apoptosis; embryo; neoplasm proteins; cell line; down-regulation; immunoglobulin enhancer binding protein; caspase 3; enzyme activation; survivin; animalia; transcription factors; nuclear proteins; gene expression regulation; dna; gene repression; tumor suppressor proteins; western blotting; transactivation; fibroblast; cell cycle g2 phase; dna microarray; procaspase 3; repressor proteins; tumor necrosis factor; promyelocytic leukemia protein; cells; microtubule-associated proteins; caspase 7; receptors, retinoic acid; promoter regions (genetics); trans-activation (genetics); humans; human; priority journal; article; promyelocytic leukemia protein 4 |
| Journal Title: | Journal of Biological Chemistry |
| Volume: | 279 |
| Issue: | 3 |
| ISSN: | 0021-9258 |
| Publisher: | American Society for Biochemistry and Molecular Biology |
| Date Published: | 2004-01-16 |
| Start Page: | 1838 |
| End Page: | 1844 |
| Language: | English |
| DOI: | 10.1074/jbc.M310987200 |
| PROVIDER: | scopus |
| PUBMED: | 14597622 |
| DOI/URL: | |
| Notes: | J. Biol. Chem. -- Cited By (since 1996):35 -- Export Date: 16 June 2014 -- CODEN: JBCHA -- Source: Scopus |
Altmetric
Citation Impact
BMJ Impact Analytics
MSK Authors
Related MSK Work