Regulation of DNA binding and transactivation in p53 by nuclear localization and phosphorylation

Oncogene
J D MartinezG T Bowden

Abstract

Compelling evidence indicates that p53 acts as a transcription factor and that this activity is regulated by several factors including subcellular localization and phosphorylation status of the protein. To learn more about how these two processes determine whether p53 becomes activated, we studied the temperature sensitive murine p53, p53val135. At nonpermissive temperatures, p53val135 remains sequestered in the cytoplasm of cells which express it. Electrophoretic mobility shift assays demonstrated that, under these conditions, the protein lacked DNA binding activity. However, by shifting to the permissive temperature, p53val135 became concentrated in the nucleus, hyperphosphorylated, and had acquired the ability to bind DNA in a sequence specific manner. This was accompanied by the induction of two p53 regulated genes, mdm2 and p21waf1, which indicated that p53val135 had become an active transcription factor. Two dimensional gel electrophoresis and tryptic peptide mapping showed that entry into the nucleus resulted in the appearance of new phosphorylated isoforms and that the protein had become extensively phosphorylation at the N-terminus. Notably, phosphorylation at the N-terminus occurred only in the nucleus, whereas phosph...Continue Reading

Citations

Sep 7, 1999·In Vitro Cellular & Developmental Biology. Animal·P A KnepperD G McLone
Mar 1, 2006·International Journal of Peptide Research and Therapeutics·Peter M Fischer
Jul 17, 1998·The Journal of Pathology·V SaveP A Hall
May 18, 1999·The Journal of Biological Chemistry·C HuangZ Dong
Sep 20, 2000·The Journal of Biological Chemistry·C CainC Prives
Apr 23, 1999·The Journal of Biological Chemistry·C HuangZ Dong

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