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Mol Cancer Res. 2009 Aug;7(8):1408-15. doi: 10.1158/1541-7786.MCR-08-0533. Epub 2009 Aug 11.

NGFI-B nuclear orphan receptor Nurr1 interacts with p53 and suppresses its transcriptional activity.

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1
Laboratory of Molecular Neuropathology, Hefei National Laboratory for Physical Sciences at Microscale and School of Life Sciences, University of Science and Technology of China, Hefei, Anhui 230027, People's Republic of China.

Abstract

Nurr1 is a member of the NGFI-B nuclear orphan receptor family which includes two other members, Nur77 and Nor-1. Nurr1 is essential for the development and survival of dopaminergic neurons. It was reported that Nurr1 has antiapoptotic functions, however, the mechanisms by which Nurr1 mediates these effects remain unknown. Here, we show that overexpression of Nurr1 decreases Bax expression whereas knockdown of Nurr1 increases Bax expression. Nurr1 also interacts with p53 and represses its assembly. Furthermore, Nurr1 represses p53 transcriptional activity in interaction-dependent and dose-dependent manners. Moreover, Nurr1 protects cells from doxorubicin-induced apoptosis. These findings provide evidence that Nurr1 promotes cell survival through its interacting with and repressing p53, thus implicating that Nurr1 may play an important role in carcinogenesis and other diseases.

PMID:
19671681
DOI:
10.1158/1541-7786.MCR-08-0533
[Indexed for MEDLINE]
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