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|Title:||c-Jun regulates the stability and activity of the p53 homologue, p73|
|Citation:||Toh, W.H., Siddique, M.M., Boominathan, L., Lin, K.W., Sabapathy, K. (2004-10-22). c-Jun regulates the stability and activity of the p53 homologue, p73. Journal of Biological Chemistry 279 (43) : 44713-44722. ScholarBank@NUS Repository. https://doi.org/10.1074/jbc.M407672200|
|Abstract:||Chemotherapeutic drugs and stress signals activate p73, the structural and functional homologue of p53, both by transcriptional activation and post-translational modifications. However, cisplatin, a DNA damage-inducing chemotherapeutic agent, is thought to regulate p73 only by affecting its stability through mechanisms involving the MLH-1/c-Abl signaling cascade. Here we show that c-Jun, a component of the AP-1 family of transcription factors, contributes to p73 induction by cisplatin. c-jun-/- cells are defective in p73 induction, and ectopic c-Jun expression augments p73 levels. c-Jun-mediated accumulation of p73 requires the transactivation activity of c-Jun and occurs in a c-Abl-and Mdm2-independent manner. c-Jun expression increases p73 half-life by preventing it from proteasome-mediated degradation, resulting in the potentiation of p73-mediated transcriptional activity. Moreover, mouse fibroblasts lacking c-Jun are resistant to cisplatin-induced apoptosis, and reintroduction of c-Jun restores p73 activation and sensitivity to cisplatin. Furthermore, p73-mediated apoptosis is abrogated in c-jun -/- cells. Together, these findings demonstrate a possible role for c-Jun in regulating p73 function and highlight the importance of the cooperativity between transcription factors in potentiating apoptosis.|
|Source Title:||Journal of Biological Chemistry|
|Appears in Collections:||Staff Publications|
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