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Title: Stra6, a retinoic acid-responsive gene, participates in p53-induced apoptosis after DNA damage.
Authors: Carrera, Samantha
Cuadrado-Castano, S
Samuel, Jesvin
Jones, G. Don
Villar, E
Lee, S W
Macip, Salvador
First Published: Jul-2013
Publisher: Nature Publishing Group For Congregazione dei Figli dell'Immacolata Concezione (CFIC), Istituto di Ricovero e Cura a Carattere Scientifico, Istituto Dermopatico dell'Immacolata (IDI-IRCCS)
Citation: Cell Death Differ, 2013, 20 (7), pp. 910-919
Abstract: Stra6 is the retinoic acid (RA)-inducible gene encoding the cellular receptor for holo-retinol binding protein. This transmembrane protein mediates the internalization of retinol, which then upregulates RA-responsive genes in target cells. Here, we show that Stra6 can be upregulated by DNA damage in a p53-dependent manner, and it has an important role in cell death responses. Stra6 expression induced significant amounts of apoptosis in normal and cancer cells, and it was also able to influence p53-mediated cell fate decisions by turning an initial arrest response into cell death. Moreover, inhibition of Stra6 severely compromised p53-induced apoptosis. We also found that Stra6 induced mitochondria depolarization and accumulation of reactive oxygen species, and that it was present not only at the cellular membrane but also in the cytosol. Finally, we show that these novel functions of Stra6 did not require downstream activation of RA signalling. Our results present a previously unknown link between the RA and p53 pathways and provide a rationale to use retinoids to upregulate Stra6, and thus enhance the tumour suppressor functions of p53. This may have implications for the role of vitamin A metabolites in cancer prevention and treatment.
DOI Link: 10.1038/cdd.2013.14
ISSN: 1350-9047
eISSN: 1476-5403
Version: Post-print
Status: Peer-reviewed
Type: Journal Article
Rights: Copyright the Authors. Archived with reference to SHERPA/RoMEO
Description: PMCID: PMC3679452
Appears in Collections:Published Articles, Dept. of Biochemistry

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