{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\n CASTOR1 is a cytosolic arginine sensor that plays a pivotal role in regulating mTOR complex 1 (mTORC1) signaling in response to changes in intracellular arginine levels. In conditions of arginine deprivation, CASTOR1 interacts with the GATOR2 complex to maintain mTORC1 inhibition, whereas arginine binding to CASTOR1 (with a dissociation constant in the micromolar range) disrupts this interaction, thereby enabling mTORC1 activation."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "1", "end_ref": "3"}]}, {"type": "t", "text": " Structural studies have revealed that CASTOR1 homodimerizes and contains ACT domains that mediate arginine binding and allosteric regulation of its association with GATOR2."}]}, {"type": "t", "text": "\n "}, {"type": "p", "children": [{"type": "t", "text": "\n Beyond its role in nutrient sensing, CASTOR1 is subject to regulatory mechanisms that affect mTORC1 activity in pathological contexts. For instance, in some cancers, reduced expression or forced degradation of CASTOR1 via ubiquitination or viral miRNAs (e.g., in the context of Kaposi’s sarcoma-associated herpesvirus) leads to a constitutive activation of mTORC1 signaling, promoting tumor progression."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "4", "end_ref": "7"}]}, {"type": "t", "text": " Moreover, in certain stress environments, such as heat stress in mammary epithelial cells, upregulation of CASTOR1 has been associated with increased apoptosis and alterations in milk synthesis, highlighting its role in cellular stress adaptation."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "8"}]}, {"type": "t", "text": "\n "}]}, {"type": "t", "text": "\n "}, {"type": "p", "children": [{"type": "t", "text": "\n In summary, CASTOR1 functions as an essential arginine sensor that links amino acid availability to mTORC1 activity, thereby impacting cell growth, metabolism, and stress responses. Its modulation—whether by nutrient binding, post-translational modifications, or changes in expression—represents a critical control point in both normal physiology and disease states, making it a promising target for therapeutic intervention in mTORC1‐dysregulated conditions.\n "}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Lynne Chantranupong, Sonia M Scaria, Robert A Saxton, et al. 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