DNA Damage-Induced ROR alpha Is Crucial for p53 Stabilization and Increased Apoptosis

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A critical component of the DNA damage response is the p53 tumor suppressor, and aberrant p53 function leads to uncontrolled cell proliferation and malignancy. Several molecules have been shown to regulate p53 stability; however, genome-wide systemic approaches for determining the affected, specific downstream target genes have not been extensively studied. Here, we first identified an orphan nuclear receptor, ROR alpha, as a direct target gene of p53, which contains functional p53 response elements. The functional consequences of DNA damage-induced ROR alpha are to stabilize p53 and activate p53 transcription in a HAUSP/Usp7-dependent manner. Interestingly, microarray analysis revealed that ROR alpha-mediated p53 stabilization leads to the activation of a subset of p53 target genes that are specifically involved in apoptosis. We further confirmed that ROR alpha enhances p53-dependent, in vivo apoptotic function in the Drosophila model system. Together, we determined that ROR alpha is a p53 regulator that exerts its role in increased apoptosis via p53.
Publisher
CELL PRESS
Issue Date
2011-12
Language
English
Article Type
Article
Keywords

TUMOR-SUPPRESSOR P53; REGULATES P53; MDM2; GENE; UBIQUITINATION; DEGRADATION; PROMOTES; DROSOPHILA-P53; PROTEASOME; STABILITY

Citation

MOLECULAR CELL, v.44, no.5, pp.797 - 810

ISSN
1097-2765
DOI
10.1016/j.molcel.2011.09.023
URI
http://hdl.handle.net/10203/102474
Appears in Collection
BS-Journal Papers(저널논문)
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