Dissecting the ROS-regulatory mechanisms of Sestrin 2-dependent mTORC1 suppression (A10)

• Subject Area: Hematology, Oncology ; Pharmacology
• Term: from 2009 to 2020
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 61867463

Sestrin 2 (Sesn2) is a cellular stress protein, which recently was described to function as an amino acid sensor to regulate mTORC1 activity in cooperation with the GATOR complex. In preliminiary work, we could show that Sesn2/GATOR additionally functions as a ROS-sensitive suppressor of mTORC1 signaling and modulates hematopoietic stem cell function. Therefore, we will unravel Sesn2-dependent mechanisms coupling cellular redox homeostasis, metabolism of amino acids and putative (patho-)physiological impacts on hematopoietic stem cell function and leukemia development.

• DFG Programme: Collaborative Research Centres
• Subproject of: SFB 815: Redox-Regulation: Generating Systems and Functional Consequences
• Applicant Institution: Goethe-Universität Frankfurt am Main
• Project Heads: Dr. Nina Kurrle; Professor Dr. Harald von Melchner, Ph.D., until 12/2016; Professor Dr. Hubert Serve