Simultaneous phosphorylation of p53 at serine 15 and 20 induces apoptosis in human glioma cells by increasing expression of pro-apoptotic genes
Journal of Neuro-Oncology, ISSN: 0167-594X, Vol: 92, Issue: 3 SPEC. ISS., Page: 357-371
2009
- 28Citations
- 16Captures
Metric Options: CountsSelecting the 1-year or 3-year option will change the metrics count to percentiles, illustrating how an article or review compares to other articles or reviews within the selected time period in the same journal. Selecting the 1-year option compares the metrics against other articles/reviews that were also published in the same calendar year. Selecting the 3-year option compares the metrics against other articles/reviews that were also published in the same calendar year plus the two years prior.
Example: if you select the 1-year option for an article published in 2019 and a metric category shows 90%, that means that the article or review is performing better than 90% of the other articles/reviews published in that journal in 2019. If you select the 3-year option for the same article published in 2019 and the metric category shows 90%, that means that the article or review is performing better than 90% of the other articles/reviews published in that journal in 2019, 2018 and 2017.
Citation Benchmarking is provided by Scopus and SciVal and is different from the metrics context provided by PlumX Metrics.
Example: if you select the 1-year option for an article published in 2019 and a metric category shows 90%, that means that the article or review is performing better than 90% of the other articles/reviews published in that journal in 2019. If you select the 3-year option for the same article published in 2019 and the metric category shows 90%, that means that the article or review is performing better than 90% of the other articles/reviews published in that journal in 2019, 2018 and 2017.
Citation Benchmarking is provided by Scopus and SciVal and is different from the metrics context provided by PlumX Metrics.
Metrics Details
- Citations28
- Citation Indexes28
- 28
- CrossRef23
- Captures16
- Readers16
- 16
Article Description
Understanding the mechanism underlying p53's ability to induce cell cycle arrest versus apoptosis is critical to treating human gliomas, 70% of which contain wild-type p53. Although N-terminal phosphorylation results in activation of p53, the role of N-terminal phosphorylation, particularly at serines 15 and 20, in p53's ability to induce cell cycle arrest versus apoptosis remains controversial. Here we test the hypothesis that phosphorylation of serine 15 and/or 20 is causally related to p53-mediated apoptosis in human gliomas. Introduction of p53 plasmids containing alanine mutations at serine 15 or/and serine 20 (which block phosphorylation) or aspartate mutations (which mimic phosphorylation) at the same sites, implicated simultaneous phosphorylation of both sites in the induction of apoptosis. When a double phosphorylation-mimicking adenoviral p53 vector (Ad-p53-15D20D) was compared with an unphosphorylated p53 vector (Ad-p53), treatment with Ad-p53 resulted in G1-arrest, whereas Ad-p53-15D20D induced apoptosis. These effects occurred independent of phosphorylation of other N-terminal serine (i.e., serines 6, 9, 33, 37, 46) indicating that phosphorylation of S15 and S20 is sufficient for inducing apoptosis. Mechanistically, Ad-p53 was capable only of increasing the expression of p21/CIP, whereas Ad-p53-15D20D increased the binding to and expression of the pro-apoptotic genes Fas, Puma and PIG3. However, Ad-p53-15D20D did not alter the expression of Noxa, Bid, IGFBP3, PERP and Killer/DR5, suggesting that phosphorylation of S15 and S20 resulted in the expression of specific pro-apoptotic gene. In conclusion, simultaneous phosphorylation of S15 and S20 is causally associated with apoptosis, resulting in increased expression of specific p53-responsive pro-apoptotic genes. © Springer Science+Business Media, LLC. 2009.
Bibliographic Details
http://www.scopus.com/inward/record.url?partnerID=HzOxMe3b&scp=65249124123&origin=inward; http://dx.doi.org/10.1007/s11060-009-9844-1; http://www.ncbi.nlm.nih.gov/pubmed/19357962; http://link.springer.com/10.1007/s11060-009-9844-1; http://www.springerlink.com/index/10.1007/s11060-009-9844-1; http://www.springerlink.com/index/pdf/10.1007/s11060-009-9844-1; https://dx.doi.org/10.1007/s11060-009-9844-1; https://link.springer.com/article/10.1007/s11060-009-9844-1
Springer Science and Business Media LLC
Provide Feedback
Have ideas for a new metric? Would you like to see something else here?Let us know