The DOI matches its Crossref record; 2 of the 2 references it cites were found in a registry or an index.
Silencing of the Novel p53 Target Gene Snk/Plk2 Leads to Mitotic Catastrophe in Paclitaxel (Taxol)-Exposed Cells
Open accessAbstract
Loss of p53 sensitizes to antimicrotubule agents in human tumor cells, but little is known about its role during mitosis. We have identified the Polo-like kinase family member serum inducible kinase (Snk/Plk2) as a novel p53 target gene. Snk/Plk2 mutagenesis demonstrated that its kinase activity is negatively regulated by its C terminus. Small interfering RNA (siRNA)-mediated Snk/Plk2 silencing in the presence of the mitotic poisons paclitaxel (Taxol) or nocodazole significantly increased apoptosis, similar to p53 mutations, which confer paclitaxel sensitivity. Furthermore, we have demonstrated that the apoptosis due to silencing of Snk/Plk2 in the face of spindle damage occurs in mitotic cells and not in cells that have progressed to a G(1)-like state without dividing. Since siRNA directed against Snk/Plk2 promoted death of paclitaxel-treated cells in mitosis, we envision a mitotic checkpoint wherein p53-dependent activation of Snk/Plk2 prevents mitotic catastrophe following spindle damage. Finally, these studies suggest that disruption of Snk/Plk2 may be of therapeutic value in sensitizing paclitaxel-resistant tumors.
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Citations
Cites
p53 Mutations in Human Cancers
Hollstein, M., Sidransky, D., Vogelstein, B., & Harris, C. C. (1991) · Science · doi:10.1126/science.1905840 · Cited by 8,018
Vogelstein, B., Lane, D., & Levine, A. J. (2000) · Nature · doi:10.1038/35042675 · Cited by 6,607 · cited 1×
“Loss of p53 has been shown to lead to genomic instability in both normal and tumor cells ( 49 ).”
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Cited by
Transcriptional control of human p53-regulated genes
Riley, T., Sontag, E., Chen, P., & Levine, A. (2008) · Nature Reviews Molecular Cell Biology · doi:10.1038/nrm2395 · Cited by 1,921
Cell death by mitotic catastrophe: a molecular definition
Castedo, M., Perfettini, J.-L., Roumier, T., Andreau, K., Medema, R., & Kroemer, G. (2004) · Oncogene · doi:10.1038/sj.onc.1207528 · Cited by 1,269
Census and evaluation of p53 target genes
Fischer, M. (2017) · Oncogene · doi:10.1038/onc.2016.502 · Cited by 971
Shared and separate functions of polo-like kinases and aurora kinases in cancer
Lens, S. M. A., Voest, E. E., & Medema, R. H. (2010) · Nature Reviews Cancer · doi:10.1038/nrc2964 · Cited by 597
The transcription factor p53: Not a repressor, solely an activator.
Fischer, M., Steiner, L., & Engeland, K. (2014) · Cell Cycle · doi:10.4161/15384101.2014.949083 · Cited by 153
Metadata
- Authors
- Burns, T. F., Fei, P., Scata, K. A., Dicker, D. T., & El-Deiry, W. S.
- Venue
- Molecular and Cellular Biology
- Publisher
- Informa UK Limited
- Published
- 2003-08-01
- Volume
- 23
- Issue
- 16
- Pages
- 5556-5571
- ISSN
- 0270-7306 (ISSN-L)
- 1098-5549
- OpenAlex
- W2170002512
- Cited by
- 219
- References
- 2
- FWCI
- 5.14
- Type
- journal article
- Language
- en
- Open access
- green
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- Burns, T. F., Fei, P., Scata, K. A., Dicker, D. T., & El-Deiry, W. S. (2003). Silencing of the Novel p53 Target Gene Snk/Plk2 Leads to Mitotic Catastrophe in Paclitaxel (Taxol)-Exposed Cells. Molecular and Cellular Biology. https://doi.org/10.1128/mcb.23.16.5556-5571.2003
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