New p53-Dependent Gene Cooperates With p53 in Tumor-Suppressor Functions

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The TP53 tumor-suppressor gene influences genomic stability, apoptosis, autophagy, response to stress, and DNA damage, and identification of new p53-target genes could help elucidate mechanisms through which p53 controls cell integrity and response to damage. As reported in Journal of the National Cancer Institute, Polato and colleagues have identified DRAGO (drug-activated gene overexpressed, KIAA0247) as a new p53-responsive gene inducible by treatment with DNA-damaging agents.

DRAGO is highly conserved, with ectopic overexpression resulting in suppression of tumor growth and increased cell death. DRAGO−/− mice are viable and have no macroscopic alterations. In p53−/− or p53+/− mice, deletion of both DRAGO alleles significantly accelerated tumor development and reduced lifespan compared with p53−/− or p53+/− mice with wild-type DRAGO alleles.

DRAGO mRNA levels were significantly reduced in advanced-stage vs early-stage ovarian tumors, although no mutations were found in several human tumors. It was shown that DRAGO expression is regulated at the transcriptional level by p53 (and p73) and methylation-dependent control and at the post-transcriptional level by miRNAs.

The investigators concluded, “DRAGO represents a new p53-dependent gene highly regulated in human cells and whose expression cooperates with p53 in tumor suppressor functions.”  ■

Polato F, et al: J Natl Cancer Inst 106(4):dju053, 2014.