The Function of SESN1
Functions as an intracellular leucine sensor that negatively regulates the TORC1 signaling pathway through the GATOR complex. In absence of leucine, binds the GATOR subcomplex GATOR2 and prevents TORC1 signaling. Binding of leucine to SESN2 disrupts its interaction with GATOR2 thereby activating the TORC1 signaling pathway (PubMed:25263562, PubMed:26449471). This stress-inducible metabolic regulator may also play a role in protection against oxidative and genotoxic stresses (By similarity). May positively regulate the transcription by NFE2L2 of genes involved in the response to oxidative stress by facilitating the SQSTM1-mediated autophagic degradation of KEAP1 (PubMed:23274085). May have an alkylhydroperoxide reductase activity born by the N-terminal domain of the protein (By similarity). Was originally reported to contribute to oxidative stress resistance by reducing PRDX1 (PubMed:15105503). However, this could not be confirmed.
Protein names
Recommended name:
Sestrin-1Alternative name(s):
p53-regulated protein PA26Top Gene-Substance Interactions
Substances That Increase SESN1
Substances | Interaction | Organism | Category |
Substances That Decrease SESN1
Substances | Interaction | Organism | Category |
Conditions with Increased Gene Activity
Condition | Change (log2fold) | Comparison | Species | Experimental variables | Experiment name |
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Conditions with Decreased Gene Activity
Condition | Change (log2fold) | Comparison | Species | Experimental variables | Experiment name |
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Technical
The following transcription factors affect gene expression:
Tissue specificity:
Widely expressed.
Induction:
Isoform T2 and isoform T3 are induced by genotoxic stress (UV, gamma-irradiation and cytotoxic drugs) in a p53/TP53-dependent manner. Isoform T1 is not induced by p53/TP53.
Molecular Function:
Biological Processes:
- Cellular Oxidant Detoxification
- Cellular Response To Amino Acid Stimulus
- Negative Regulation Of Torc1 Signaling
- Reactive Oxygen Species Metabolic Process
- Regulation Of Response To Reactive Oxygen Species