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.
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.
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.