RNF167 and CASTOR1 as Novel mTOR Targets

Oncology

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.

Project Team

Prof. Shou-Jiang Gao
Prof. Shou-Jiang Gao

Institutions

University of Pittsburg
University of Pittsburg
US

Project Status

Clinical Stage
Preclinical
Patent Status
Patent not filed

Funding Opportunity

Opportunity type
Funding requested
$0
Funding allocated
$0

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.

Project Details

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.