Che‐1‐induced inhibition of mTOR pathway enables stress‐induced autophagy |
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| Authors: | 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 |
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| Affiliation: | 1. Epigenetics Laboratory, Molecular Medicine Area, Regina Elena National Cancer Institute, Rome, Italy;2. Department of Biotechnological and Applied Clinical Sciences, University of L'Aquila, L'Aquila, Italy;3. Translational Oncogenomic Laboratory, Molecular Medicine Area, Regina Elena National Cancer Institute, Rome, Italy;4. Pathology and Myeloma Units, Molecular Oncology Division, San Raffaele Scientific Institute, Milan, Italy;5. Molecular Oncogenesis Laboratory, Regina Elena National Cancer Institute, Rome, Italy;6. Division of Hematology, Department of Cellular Biotechnologies and Hematology, “Sapienza” University, Rome, Italy;7. Laboratory of Pharmacology, Department of Health Sciences, University of Milan, Milan, Italy;8. HPC CINECA, Rome, Italy;9. Hematology Laboratory, Regina Elena National Cancer Institute, Rome, Italy;10. Comprehensive Cancer Center, Mayo Clinic Arizona, Scottsdale, AZ, USA;11. Functional Genomics of Cancer Unit, Molecular Oncology Division, San Raffaele Scientific Institute, Milan, Italy;12. Institute of Molecular Biology and Pathology, CNR, Department of Molecular Medicine, “Sapienza” University, Rome, Italy |
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| Abstract: | ![]()
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. |
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| Keywords: |
mTOR
autophagy multiple myeloma Che‐1 |
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