Gene interactions and pathways from curated databases and text-mining
Cell 2008, PMID: 18692468

p53 target genes sestrin1 and sestrin2 connect genotoxic stress and mTOR signaling.

Budanov, Andrei V; Karin, Michael

The tumor suppressor p53 is activated upon genotoxic and oxidative stress and in turn inhibits cell proliferation and growth through induction of specific target genes. Cell growth is positively regulated by mTOR, whose activity is inhibited by the TSC1:TSC2 complex. Although genotoxic stress has been suggested to inhibit mTOR via p53-mediated activation of mTOR inhibitors, the precise mechanism of this link was unknown. We now demonstrate that the products of two p53 target genes, Sestrin1 and Sestrin2, activate the AMP-responsive protein kinase (AMPK) and target it to phosphorylate TSC2 and stimulate its GAP activity, thereby inhibiting mTOR. Correspondingly, Sestrin2-deficient mice fail to inhibit mTOR signaling upon genotoxic challenge. Sestrin1 and Sestrin2 therefore provide an important link between genotoxic stress, p53 and the mTOR signaling pathway.

Document information provided by NCBI PubMed

Text Mining Data

mTOR ⊣ p53: " Although genotoxic stress has been suggested to inhibit mTOR via p53 mediated activation of mTOR inhibitors, the precise mechanism of this link was unknown "

mTOR ⊣ AMP-responsive protein kinase (AMPK): " We now demonstrate that the products of two p53 target genes, Sestrin1 and Sestrin2, activate the AMP-responsive protein kinase (AMPK) and target it to phosphorylate TSC2 and stimulate its GAP activity, thereby inhibiting mTOR "

mTOR ⊣ GAP: " We now demonstrate that the products of two p53 target genes, Sestrin1 and Sestrin2, activate the AMP-responsive protein kinase (AMPK) and target it to phosphorylate TSC2 and stimulate its GAP activity, thereby inhibiting mTOR "

Manually curated Databases

No curated data.