| First Author | Leslie PL | Year | 2018 |
| Journal | Cell Rep | Volume | 24 |
| Issue | 6 | Pages | 1484-1495 |
| PubMed ID | 30089260 | Mgi Jnum | J:276406 |
| Mgi Id | MGI:6316512 | Doi | 10.1016/j.celrep.2018.07.010 |
| Citation | Leslie PL, et al. (2018) p53 Regulates the Expression of LRP1 and Apoptosis through a Stress Intensity-Dependent MicroRNA Feedback Loop. Cell Rep 24(6):1484-1495 |
| abstractText | Understanding how p53 activates certain gene programs and not others is critical. Here, we identify low-density lipoprotein receptor-related protein 1 (LRP1), a transmembrane endocytic receptor, as a p53 target gene. We show that, although LRP1 transcript expression is upregulated in response to both sub-lethal and lethal doses of p53-activating stress, LRP1 protein is only upregulated in response to sub-lethal stress. Interestingly, lethal doses of p53-activating stress inhibit LRP1 de novo translation through an miRNA-based translational repression mechanism. We show that the p53-regulated miRNAs miR-103 and miR-107 are significantly upregulated by lethal doses of stress, resulting in suppression of LRP1 translation and cell death. Our results define a negative feedback loop involving the p53-regulated coding gene LRP1 and p53-regulated miRNA genes. These findings provide mechanistic insight into the selective expression of p53 target genes in response to different stress intensities to elicit either cell survival or cell death. |
