FOXP1 phosphorylation/O-GlcNAcylation in regulating ATR activation in response to replication stress

ABSTRACT: ATR signaling is essential in sensing and responding to the replication stress; as such, any defects can impair cellular function and survival. ATR itself is activated via tightly regulated mechanisms. Here, we identify FOXP1, a forkhead-box-containing transcription factor, as a regulator coordinating ATR activation. We show that, unlike its role as a transcription factor, FOXP1 functions as a scaffold and directly binds to RPA-ssDNA and ATR-ATRIP complexes, facilitating the recruitment and activation of ATR. This process is regulated by FOXP1 O-GlcNAcylation¬¬, which represses its interaction with ATR, while CHK1-mediated phosphorylation of FOXP1 inhibits its O-GlcNAcylation upon replication stress. Supporting the physiological relevance of this loop, we find pathogenic FOXP1 mutants iden

SUBMITTER: Dr. Xuefei Zhu 

PROVIDER: S-SCDT-10_1038-S44318-024-00323-X | biostudies-other |

REPOSITORIES: biostudies-other