Multilayered control of protein turnover by torc1 and atg1

Hu, Zehan; Raucci, Serena; Jaquenoud, Malika; Hatakeyama, Riko; Stumpe, Michael; Rohr, Rudolf P.; Reggiori, Fulvio; De Virgilio, Claudio; Dengjel, Jörn

doi:10.1016/j.celrep.2019.08.069

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Multilayered control of protein turnover by torc1 and atg1

Hu, Zehan Department of Biology, University of Fribourg, Switzerland
Raucci, Serena Department of Biology, University of Fribourg, Switzerland
Jaquenoud, Malika Department of Biology, University of Fribourg, Switzerland
Hatakeyama, Riko Department of Biology, University of Fribourg, Switzerland
Stumpe, Michael Department of Biology, University of Fribourg, Switzerland
Rohr, Rudolf P. Department of Biology, University of Fribourg, Switzerland
Reggiori, Fulvio Department of Biomedical Sciences of Cells & Systems, University of Groningen, University Medical Center Groningen, the Netherlands
De Virgilio, Claudio Department of Biology, University of Fribourg, Switzerland
Dengjel, Jörn Department of Biology, University of Fribourg, Switzerland

24.09.2019

Published in:

Cell Reports. - 2019, vol. 28, no. 13, p. 3486-3496.e6

English The target of rapamycin complex 1 (TORC1) is a master regulator of cell homeostasis, which promotes anabolic reactions and synchronously inhibits catabolic processes such as autophagy-mediated protein degradation. Its prime autophagy target is Atg13, a subunit of the Atg1 kinase complex that acts as the gatekeeper of canonical autophagy. To study whether the activities of TORC1 and Atg1 are coupled through additional, more intricate control mechanisms than simply this linear pathway, we analyzed the epistatic relationship between TORC1 and Atg1 by using quantitative phosphoproteomics. Our in vivo data, combined with targeted in vitro TORC1 and Atg1 kinase assays, not only uncover numerous TORC1 and Atg1 effectors, but also suggest distinct bi-directional regulatory feedback loops and characterize Atg29 as a commonly regulated downstream target of both TORC1 and Atg1. Thus, an exquisitely multilayered regulatory network appears to coordinate TORC1 and Atg1 activities to robustly tune autophagy in response to nutritional cues.

Faculty

Faculté des sciences et de médecine

Department

Département de Biologie

Language