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Che‐1‐induced inhibition of mTOR pathway enables stress‐induced autophagy

Author:
Agata Desantis  Tiziana Bruno  Valeria Catena  Francesca De Nicola  Frauke Goeman  Simona Iezzi  Cristina Sorino  Maurilio Ponzoni  Gianluca Bossi  Vincenzo Federico  Francesca La Rosa  Maria Rosaria Ricciardi  Elena Lesma  Paolo D'Onorio De Meo  Tiziana Castrignanò  Maria Teresa Petrucci  Francesco Pisani  Marta Chesi  P Leif Bergsagel  Aristide Floridi  Giovanni Tonon  Claudio Passananti  Giovanni Blandino  Maurizio Fanciulli  


Journal:
The EMBO Journal


Issue Date:
2015


Abstract(summary):

Mammalian target of rapamycin (mTOR) is a key protein kinase that regulates cell growth, metabolism, and autophagy to maintain cellular homeostasis. Its activity is inhibited by adverse conditions, including nutrient limitation, hypoxia, and DNA damage. In this study, we demonstrate that Che‐1, a RNA polymerase II‐binding protein activated by the DNA damage response, inhibits mTOR activity in response to stress conditions. We found that, under stress, Che‐1 induces the expression of two important mTOR inhibitors, Redd1 and Deptor, and that this activity is required for sustaining stress‐induced autophagy. Strikingly, Che‐1 expression correlates with the progression of multiple myeloma and is required for cell growth and survival, a malignancy characterized by high autophagy response.


Page:
1214-1230


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