| Autor: |
Leslie, Patrick L., Franklin, Derek A., Liu, Yong, Zhang, Yanping |
| Zdroj: |
Cell Reports; Aug2018, Vol. 24 Issue 6, p1484-1495, 12p |
| Abstrakt: |
Summary 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. [ABSTRACT FROM AUTHOR] |
| Databáze: |
Complementary Index |
| Externí odkaz: |
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