| First Author | Deng L | Year | 2015 |
| Journal | Mol Cell | Volume | 58 |
| Issue | 5 | Pages | 804-18 |
| PubMed ID | 25936802 | Mgi Jnum | J:222252 |
| Mgi Id | MGI:5644195 | Doi | 10.1016/j.molcel.2015.03.033 |
| Citation | Deng L, et al. (2015) The Ubiquitination of RagA GTPase by RNF152 Negatively Regulates mTORC1 Activation. Mol Cell 58(5):804-18 |
| abstractText | mTORC1 is essential for regulating cell growth and metabolism in response to various environmental stimuli. Heterodimeric Rag GTPases are required for amino-acid-mediated mTORC1 activation at the lysosome. However, the mechanism by which amino acids regulate Rag activation remains not fully understood. Here, we identified the lysosome-anchored E3 ubiquitin ligase RNF152 as an essential negative regulator of the mTORC1 pathway by targeting RagA for K63-linked ubiquitination. RNF152 interacts with and ubiquitinates RagA in an amino-acid-sensitive manner. The mutation of RagA ubiquitination sites abolishes this effect of RNF152 and enhances the RagA-mediated activation of mTORC1. Ubiquitination by RNF152 generates an anchor on RagA to recruit its inhibitor GATOR1, a GAP complex for Rag GTPases. RNF152 knockout results in the hyperactivation of mTORC1 and protects cells from amino-acid-starvation-induced autophagy. Thus, this study reveals a mechanism for regulation of mTORC1 signaling by RNF152-mediated K63-linked polyubiquitination of RagA. |
