Affiliation:
1. Istituto di Biologia e Patologia Molecolari del CNR, c/o Dipartimento di Biologia e Biotecnologie, Sapienza Università di Roma, 00185 Roma, Italy
Abstract
The evolutionarily conserved target of rapamycin (TOR) serine/threonine kinase controls eukaryotic cell growth, metabolism and survival by integrating signals from the nutritional status and growth factors. TOR is the catalytic subunit of two distinct functional multiprotein complexes termed mTORC1 (mechanistic target of rapamycin complex 1) and mTORC2, which phosphorylate a different set of substrates and display different physiological functions. Dysregulation of TOR signaling has been involved in the development and progression of several disease states including cancer and diabetes. Here, we highlight how genetic and biochemical studies in the model system Drosophila melanogaster have been crucial to identify the mTORC1 and mTORC2 signaling components and to dissect their function in cellular growth, in strict coordination with insulin signaling. In addition, we review new findings that involve Drosophila Golgi phosphoprotein 3 in regulating organ growth via Rheb-mediated activation of mTORC1 in line with an emerging role for the Golgi as a major hub for mTORC1 signaling.
Funder
Fondazione AIRC per la Ricerca sul Cancro
Italian Ministry of University and Research
Reference149 articles.
1. Two TOR complexes, only one of which is rapamycin sensitive, have distinct roles in cell growth control;Loewith;Mol. Cell,2002
2. mTOR Signaling in Growth, Metabolism, and Disease;Saxton;Cell,2017
3. mTOR at the nexus of nutrition, growth, ageing and disease;Liu;Nat. Rev. Mol. Cell Biol.,2020
4. Rapamycin 10. (AY-22,989), a new antifungal antibiotic I. Taxonomy of the producing streptomycete and isolation of the active principle;Vezina;J. Antibiot.,1975
5. Inhibition of the immune response by rapamycin, a new antifungal antibiotic;Martel;Can. J. Physiol. Pharmacol.,1977