| First Author | Frazier DP | Year | 2012 |
| Journal | Cancer Res | Volume | 72 |
| Issue | 7 | Pages | 1740-50 |
| PubMed ID | 22331460 | Mgi Jnum | J:184938 |
| Mgi Id | MGI:5426757 | Doi | 10.1158/0008-5472.CAN-11-2410 |
| Citation | Frazier DP, et al. (2012) Dmp1 physically interacts with p53 and positively regulates p53's stability, nuclear localization, and function. Cancer Res 72(7):1740-50 |
| abstractText | The transcription factor Dmp1 is a Ras/HER2-activated haplo-insufficient tumor suppressor that activates the Arf/p53 pathway of cell-cycle arrest. Recent evidence suggests that Dmp1 may activate p53 independently of Arf in certain cell types. Here, we report findings supporting this concept with the definition of an Arf-independent function for Dmp1 in tumor suppression. We found that Dmp1 and p53 can interact directly in mammalian cells via the carboxyl-terminus of p53 and the DNA-binding domain of Dmp1. Expression of Dmp1 antagonized ubiquitination of p53 by Mdm2 and promoted nuclear localization of p53. Dmp1-p53 binding significantly increased the level of p53, independent of the DNA-binding activity of Dmp1. Mechanistically, p53 target genes were activated synergistically by the coexpression of Dmp1 and p53 in p53(-/-);Arf(-/-) cells, and genotoxic responses of these genes were hampered more dramatically in Dmp1(-/-) and p53(-/-) cells than in Arf(-/-) cells. Together, our findings identify a robust new mechanism of p53 activation mediated by direct physical interaction between Dmp1 and p53. |
