When cells are challenged by genotoxic stress, the tumor suppressor protein p53 promotes adaptive responses, including cell cycle arrest, DNA repair, or apoptosis. How these distinct fates are specified through an action of p53 protein is not known. It has been suggested that p53 levels, its post-translational modifications or the cell’s genetic background aid p53 in deciding cells’ fate. As a transcription factor, additional evidence indicates that differences in the DNA-binding ability of p53 protein to its response elements are also important determinants of whether p53 will activate growth arrest genes or apoptotic genes. Here we utilized a set of mutant cell lines which, unlike the parental A1-5 cell line which expresses a mouse tsp53 and becomes growth arrested at 32°C, are capable of growth at this same incubation temperature. We found that the tsp53 in the two mutant cell lines, ALTR-17 and ALTR-24, could induce expression of p21, the principle growth arrest gene induced by p53, although to a lesser extent than in parental cells. Interestingly, evaluation of the conformation of tsp53 using conformation-specific antibodies showed that the protein, which we showed could induce expression of p21 reporter construct, existed in different forms which were found to bind DNA using ChIP assays. We also showed, using microarray technology, that the different forms of p53 are capable of inducing/repressing various sets p53-inducible genes. We conclude that the tsp53 may stably exist in various forms capable of binding DNA and decide cell fate through a p53 transcription-dependent pathway.
| Identifer | oai:union.ndltd.org:arizona.edu/oai:arizona.openrepository.com:10150/193992 |
| Date | January 2006 |
| Creators | Mayelzadeh, Foroozan |
| Contributors | Martinez, Jesse D., Martinez, Jesse D., Bowden, Timothy G., Nelson, Mark, Futscher, Bernard, Chen, Qin |
| Publisher | The University of Arizona. |
| Source Sets | University of Arizona |
| Language | English |
| Detected Language | English |
| Type | text, Electronic Dissertation |
| Rights | Copyright © is held by the author. Digital access to this material is made possible by the University Libraries, University of Arizona. Further transmission, reproduction or presentation (such as public display or performance) of protected items is prohibited except with permission of the author. |
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