5i2c

Structural highlights

Function

CAST1_HUMAN Functions as an intracellular arginine sensor within the amino acid-sensing branch of the TORC1 signaling pathway (PubMed:26972053, PubMed:27487210, PubMed:33594058). As a homodimer or a heterodimer with CASTOR2, binds and inhibits the GATOR subcomplex GATOR2 and thereby mTORC1 (PubMed:26972053, PubMed:27487210, PubMed:33594058). Binding of arginine to CASTOR1 allosterically disrupts the interaction of CASTOR1-containing dimers with GATOR2 which can in turn activate mTORC1 and the TORC1 signaling pathway (PubMed:26972053, PubMed:27487210, PubMed:33594058).^{[1] [2] [3]}

References

1. ↑ Chantranupong L, Scaria SM, Saxton RA, Gygi MP, Shen K, Wyant GA, Wang T, Harper JW, Gygi SP, Sabatini DM. The CASTOR Proteins Are Arginine Sensors for the mTORC1 Pathway. Cell. 2016 Mar 24;165(1):153-64. doi: 10.1016/j.cell.2016.02.035. Epub 2016 Mar, 10. PMID:26972053 doi:http://dx.doi.org/10.1016/j.cell.2016.02.035
2. ↑ Saxton RA, Chantranupong L, Knockenhauer KE, Schwartz TU, Sabatini DM. Mechanism of arginine sensing by CASTOR1 upstream of mTORC1. Nature. 2016 Aug 11;536(7615):229-33. PMID:27487210 doi:http://dx.doi.org/10.1038/nature19079
3. ↑ Li T, Wang X, Ju E, da Silva SR, Chen L, Zhang X, Wei S, Gao SJ. RNF167 activates mTORC1 and promotes tumorigenesis by targeting CASTOR1 for ubiquitination and degradation. Nat Commun. 2021 Feb 16;12(1):1055. PMID:33594058 doi:10.1038/s41467-021-21206-3