SESN1

This gene encodes a member of the sestrin family. Sestrins are induced by the p53 tumor suppressor protein and play a role in the cellular response to DNA damage and oxidative stress. The encoded protein mediates p53 inhibition of cell growth by activating AMP-activated protein kinase, which results in the inhibition of the mammalian target of rapamycin protein. The encoded protein also plays a critical role in antioxidant defense by regenerating overoxidized peroxiredoxins, and the expression of this gene is a potential marker for exposure to radiation. Alternatively spliced transcript variants encoding multiple isoforms have been observed for this gene.

Sestrin 1

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).
Moreover, may prevent the accumulation of reactive oxygen species (ROS) through the 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 (By similarity).

Biological Process cellular oxidant detoxificationManual Assertion Based On ExperimentIMP:UniProtKB
Biological Process cellular response to amino acid starvationManual Assertion Based On ExperimentIMP:UniProtKB
Biological Process cellular response to glucose starvationManual Assertion Based On ExperimentIMP:UniProtKB
Biological Process cellular response to leucineManual Assertion Based On ExperimentIBA:GO_Central
Biological Process cellular response to leucine starvationManual Assertion Based On ExperimentIBA:GO_Central
Biological Process negative regulation of TORC1 signalingManual Assertion Based On ExperimentIMP:UniProtKB
Biological Process positive regulation of macroautophagyManual Assertion Based On ExperimentIBA:GO_Central
Biological Process reactive oxygen species metabolic processManual Assertion Based On ExperimentIMP:UniProtKB
Biological Process regulation of response to reactive oxygen speciesIEA:InterPro

Nucleus
Cytoplasm