RNF167 and CASTOR1 as Novel mTOR Targets
AKT-mediated phosphorylation of CASTOR1 significantly increases its binding to RNF167, revealing a novel mTORC1 regulating mechanism and potential new therapeutic targets for mTORC1-dysregulated diseases.
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Background
Several devastating diseases including cancer, diabetes, and age-related issues have been linked to dysregulation of mTORC1, a central controller of cell proliferation in response to growth factors and nutrients. The activity of mTORC1 is repressed by cytosolic arginine sensor for mTORC1 subunit 1, or CASTOR1.
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Low CASTOR1 expression is a poor prognosis marker for ten types of cancer, while high expression of the RNF167, a ligase that targets CASTOR1 for degradation, has been identified as a poor prognosis marker for five types of cancer. Researchers also demonstrated that AKT and RNF167-mediated CASTOR1 degradation activates mTORC1 and promotes breast cancer progression. AKT-mediated phosphorylation of CASTOR1 significantly increases its binding to RNF167, revealing a novel mTORC1 regulating mechanism and potential new therapeutic targets for mTORC1-dysregulated diseases.