Please use this identifier to cite or link to this item: https://doi.org/10.1074/jbc.M407672200
Title: c-Jun regulates the stability and activity of the p53 homologue, p73
Authors: Toh, W.H.
Siddique, M.M.
Boominathan, L.
Lin, K.W.
Sabapathy, K. 
Issue Date: 22-Oct-2004
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
URI: http://scholarbank.nus.edu.sg/handle/10635/115645
ISSN: 00219258
DOI: 10.1074/jbc.M407672200
Appears in Collections:Staff Publications

Show full item record
Files in This Item:
There are no files associated with this item.

SCOPUSTM   
Citations

63
checked on Jun 15, 2018

WEB OF SCIENCETM
Citations

61
checked on May 28, 2018

Page view(s)

39
checked on May 18, 2018

Google ScholarTM

Check

Altmetric


Items in DSpace are protected by copyright, with all rights reserved, unless otherwise indicated.