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Research Paper
Lyn Tyrosine Kinase Inhibits Nuclear Export of the p53 Tumor Suppressor
Xinping Ren, Cheng Cao, Liben Zhu, Kiyotsugu Yoshida, Surender Kharbanda, Ralph Weichselbaum and Donald Kufe
volume 1 | issue 6
november/december 2002Pages: 703-708
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The p53 tumor suppressor is activated in the cellular response to stress. Mdm2 inhibits p53-dependent transactivation and promotes degradation of p53 by the ubiquitin-proteosome pathway. The present studies demonstrate that p53 binds directly to the nuclear Lyn tyrosine kinase. Lyn increases p53 levels and stimulates p53-mediated transcription by a kinase-independent mechanism. The results also demonstrate that Lyn increases nuclear levels of ubiquitinated p53 by inhibiting export of p53 to the cytoplasm. In concert with these results, Lyn reverses Mdm2-mediated degradation of p53 and increases p53-dependent apoptosis. Our findings support a previously undefined role for nuclear Lyn in both activation and Mdm2-mediated regulation of p53.
We now provide open access to journal articles published online for one year or more. This article may be downloaded at the following link:
Download PDFIf the document does not open, please right-click on the link (control-click on a Macintosh) and select the option to save the file to disk.