| First Author | Chang CJ | Year | 2004 |
| Journal | J Biol Chem | Volume | 279 |
| Issue | 28 | Pages | 29841-8 |
| PubMed ID | 15090541 | Mgi Jnum | J:91671 |
| Mgi Id | MGI:3050172 | Doi | 10.1074/jbc.M401488200 |
| Citation | Chang CJ, et al. (2004) PTEN regulates Mdm2 expression through the P1 promoter. J Biol Chem 279(28):29841-8 |
| abstractText | MDM2 is an oncoprotein that controls tumorigenesis through both p53-dependent and -independent mechanisms. Mdm2 mRNA level is transcriptionally regulated by p53 in response to stress such as DNA damage, and its protein level and subcellular localization are post-translationally modulated by the AKT serine/threonine kinase. Previous studies showed that PTEN, a dual specificity phosphatase that antagonizes phosphatidylinositol 3-kinase/AKT signaling, is capable of blocking MDM2 nuclear translocation and destabilizing the MDM2 protein. Results from our current study demonstrate an additional role for PTEN in regulating MDM2 functions; PTEN modulates Mdm2 transcription and isoform selection by negatively regulating its P1 promoter. In Pten-null cell lines and prostate cancer tissues, Mdm2 P1 promoter activity is up-regulated, resulting in increased L-Mdm2 expression and enhanced p90(MDM2) isoform production. Furthermore, PTEN controls Mdm2 P1 promoter activity through its lipid phosphatase activity, independent of p53. Thus, our results provide a novel mechanism for PTEN in controlling MDM2 oncoprotein functions. |
